研究者詳細 - 成瀬　恵治

論文 - 成瀬　恵治

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TRPV2 mediates stress resilience in mouse cardiomyocytes 査読

Dong Y, Wang G, Ujihara Y, Chen Y, Yoshida M, Nakamura K, Katanosaka K, Naruse K, Katanosaka Y

Communications Biology 8 ( 1 ) 2025年5月

Stress-experienced monocytes/macrophages lose anti-inflammatory function via β2-adrenergic receptor in skin allergic inflammation 査読

Hitoshi Urakami, Soichiro Yoshikawa, Kei Nagao, Kensuke Miyake, Yuki Fujita, Ayaka Komura, Miho Nakashima, Ryusuke Umene, Shuhei Sano, Zheyu Hu, Emi Nishii, Atsushi Fujimura, Takeshi Y. Hiyama, Keiji Naruse, Hajime Karasuyama, Tsuyoshi Inoue, Mitsutoshi Tominaga, Kenji Takamori, Shin Morizane, Sachiko Miyake

Journal of Allergy and Clinical Immunology 155 ( 3 ) 865 - 879 2025年3月

Mechanical signaling through membrane tension induces somal translocation during neuronal migration 査読

Minegishi T., Hasebe H., Aoyama T., Naruse K., Takahashi Y., Inagaki N.

EMBO J 44 ( 3 ) 767 - 780 2025年2月

Ligand-independent function of β2-adrenergic receptor affects IgE-mediated Ca2+ influx in mast cells 査読

Nagao K, Yoshikawa S, Urakami H, Fujita Y, Komura A, Nakashima M, Oh-Hora M, Fujimura A, Hiyama TY, Naruse K, Morizane S, Tominaga M, Takamori K, Miyake S

Biochemical and Biophysical Research Communications 733 150595 - 150595 2024年11月

Direct Binding of Synaptopodin 2-Like Protein to Alpha-Actinin Contributes to Actin Bundle Formation in Cardiomyocytes 査読国際誌

Yamada H, Osaka H, Tatsumi N, Araki M, Abe T, Kaihara K, Takahashi K, Takashima E, Uchihashi T, Naruse K, Takei K

Cells 13 ( 16 ) 1373 - 1373 2024年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI AG

Synaptopodin 2-like protein (SYNPO2L) is localized in the sarcomere of cardiomyocytes and is involved in heart morphogenesis. However, the molecular function of SYNPO2L in the heart is not fully understood. We investigated the interaction of SYNPO2L with sarcomeric α-actinin and actin filaments in cultured mouse cardiomyocytes. Immunofluorescence studies showed that SYNPO2L colocalized with α-actinin and actin filaments at the Z-discs of the sarcomere. Recombinant SYNPO2La or SYNPO2Lb caused a bundling of the actin filaments in the absence of α-actinin and enhanced the α-actinin-dependent formation of actin bundles. In addition, high-speed atomic force microscopy revealed that SYNPO2La directly bound to α-actinin via its globular ends. The interaction between α-actinin and SYNPO2La fixed the movements of the two proteins on the actin filaments. These results strongly suggest that SYNPO2L cooperates with α-actinin during actin bundle formation to facilitate sarcomere formation and maintenance.

DOI： 10.3390/cells13161373

Human heart-on-a-chip microphysiological system comprising endothelial cells, fibroblasts, and iPSC-derived cardiomyocytes 査読

Liu Y, Kamran R, Han X, Wang M, Li Q, Lai D, Naruse K, Takahashi K

Scientific Reports 14 ( 1 ) 18063 2024年8月

Celiac and superior mesenteric ganglia removal improves glucose tolerance and reduces pancreas islet size 査読

Xu S, Inoue M, Yoshimura Y, Kondoh K, Naruse K, Hiyama TY

Neuroscience Letters 837 137919 - 137919 2024年8月

Effect of mechanical stretching stimulation on maturation of human iPS cell-derived cardiomyocytes co-cultured with human gingival fibroblasts

Wang M, Idei H, Wang C, Liang Y, Liu Y, Matsuda Y, Takahashi K, Kamioka H, Naruse K

2023年12月

担当区分：最終著者記述言語：英語出版者・発行元：Cold Spring Harbor Laboratory

Abstract

In the realm of regenerative medicine, despite the various techniques available for inducing the differentiation of induced pluripotent stem (iPS) cells into cardiomyocytes, there remains a need to enhance the efficiency of this induction process. This study aimed to improve the differentiation efficiency of iPS-derived cardiomyocytes (iPS-CMs) by incorporating mechanical stretching. Human iPS cells were co-cultured with human gingival fibroblasts (HGF) on a polydimethylsiloxane (PDMS) stretch chamber, where mechanical stretching stimulation was applied during the induction of cardiomyocyte differentiation. The maturation of iPS-CMs was assessed using qRT-PCR, immunofluorescence staining, transmission electron microscopy, and contractility comparisons. Results indicated significantly elevated gene expression levels of cardiomyocyte markers (cTnT) and the mesodermal marker (Nkx2.5) in the stretch group compared to the control group. Fluorescent immunocytochemical staining revealed the presence of cardiac marker proteins (cTnT and HCN4) in both groups, with higher protein expression in the stretch group. Additionally, sarcomere length in the stretch group was notably larger than in the control group. A significant increase in the contractility of iPS-CMs was observed in the stretch group. These findings demonstrate that mechanical stretching stimulation enhances the maturity and differentiation efficiency of iPS-CMs co-cultured with fibroblasts.

DOI： 10.1101/2023.12.15.567696

Development of lung tissue models and their applications 査読

Nalinrat Petpiroon, Woranan Netkueakul, Kanokwan Sukrak, Chen Wang, Yin Liang, Mengxue Wang, Yun Liu, Qiang Li, Rumaisa Kamran, Keiji Naruse, Sasitorn Aueviriyavit, Ken Takahashi

Life Sciences 334 122208 - 122208 2023年12月

Stretch‐induced reactive oxygen species contribute to the Frank–Starling mechanism 査読

Kaihara K, Kai H, Chiba Y, Naruse K, Iribe G

The Journal of Physiology 2023年4月

High hydrostatic pressure induces slow contraction in mouse cardiomyocytes 査読

Yamaguchi Y, Nishiyama M, Kai H, Kaneko T, Kaihara K, Iribe G, Takai A, Naruse K, Morimatsu M

Biophysical Journal 122 ( 1 ) 267 - 267 2023年1月

Live imaging of nitric oxide release in vascular endothelial cells in response to mechanical stimuli on an organ chip 査読

Takahashi K, Liu Y, Wang M, Liang Y, Naruse K

European Heart Journal 43 ( Supplement_22 ) 2022年10月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Oxford University Press (OUP)

Abstract

Background

Nitric oxide (NO), released from vascular endothelial cells in response to mechanical stimuli, regulates cardiac contractility and are also involved in the prevention of the development of cardiac hypertrophy.

Purpose

To establish an experimental system for live observation of NO release in response to mechanical stimuli on an organ chip.

Methods

Organ chips, which we used for the development of a heart-on-a-chip in the previous study [1], were used.

We seeded 300,000 human umbilical vein endothelial cells on a stretchable elastic membrane coated with Matrigel of a chip channel. Shear stress was applied to the cells by increasing flow rate of a peristaltic pump connected to the chip channel (Figure 1A). Pressure stimulus was applied by hydrostatic pressure. Stretch stimulus was applied by suction to the side ports of a chip using an electric syringe pump (Figure 1B). Cells were stained with 10 μM 4,5-diaminofluorescein diacetate for fluorescent live NO imaging.

Results

Monolayers of the endothelial cells formed intercellular junctions confirmed by CD31 staining (Figure 1C, yellow). Apparent permeability, which was measured by Texas red dye (MW 3000), was maintained at a low level of ∼3x10–6 cm/s until day 30, suggested the formation of robust intercellular junction.

When the endothelial cells were subjected to a pressure stimulus of 60 mmHg for 60 s, NO release was observed that lasted for &gt;2 minutes (Figure 2A). A peak value of 1.46±1.08 (mean ± standard deviation) times the baseline was observed 271 s after the beginning of the pressure stimulus (n=251 cells). When the cells were subjected to a 1% stretch for 60 s, a peak value of 1.29±0.33 times the baseline was observed 105 s after the beginning of the stretch stimulus (Figure 2B). A shear stress of 0.01 dyn/cm2 hardly increased NO release (1.20±0.27 times the baseline, Figure 2C).

Conclusion

The system for live NO imaging in vascular endothelial cells in response to mechanical stimuli was established using organ-on-a-chip. The heart-on-a-chip with endothelial cells will be useful in elucidating the effects of mechanical stimulus such as hypertension on the contractile function and the remodeling of the heart.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Japan Society for the Promotion of Science

DOI： 10.1093/eurheartj/ehac544.3027

High hydrostatic pressure induces slow contraction in mouse cardiomyocytes. 査読国際誌

Yamaguchi Y, Nishiyama M, Kai H, Kaneko T, Kaihara K, Iribe G, Takai A, Naruse K, Morimatsu M

Biophysical journal 2022年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Cardiomyocytes are contractile cells that regulate heart contraction. Ca2+ flux via Ca2+ channels activates actomyosin interactions, leading to cardiomyocyte contraction, which is modulated by physical factors (e.g., stretch, shear stress, and hydrostatic pressure). We evaluated the mechanism triggering slow contractions using a high-pressure microscope to characterize changes in cell morphology and intracellular Ca2+ concentration ([Ca2+]i) in mouse cardiomyocytes exposed to high hydrostatic pressures. We found that cardiomyocytes contracted slowly without an acute transient increase in [Ca2+]i, while a myosin ATPase inhibitor interrupted pressure-induced slow contractions. Furthermore, transmission electron microscopy showed that, although the sarcomere length was shortened upon the application of 20 MPa, this pressure did not collapse cellular structures such as the sarcolemma and sarcomeres. Our results suggest that pressure-induced slow contractions in cardiomyocytes are driven by the activation of actomyosin interactions without an acute transient increase in [Ca2+]i.

DOI： 10.1016/j.bpj.2022.07.016

Gravity sensing in plant and animal cells 査読

Takahashi K, Takahashi H, Furuichi T, Toyota M, Furutani-Seiki M, Kobayashi T, Watanabe-Takano H, Shinohara M, Numaga-Tomita T, Sakaue-Sawano A, Miyawaki A, Naruse K

npj Microgravity 7 ( 1 ) 2 2021年12月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media LLC

Abstract

Gravity determines shape of body tissue and affects the functions of life, both in plants and animals. The cellular response to gravity is an active process of mechanotransduction. Although plants and animals share some common mechanisms of gravity sensing in spite of their distant phylogenetic origin, each species has its own mechanism to sense and respond to gravity. In this review, we discuss current understanding regarding the mechanisms of cellular gravity sensing in plants and animals. Understanding gravisensing also contributes to life on Earth, e.g., understanding osteoporosis and muscle atrophy. Furthermore, in the current age of Mars exploration, understanding cellular responses to gravity will form the foundation of living in space.

DOI： 10.1038/s41526-020-00130-8

その他リンク： http://www.nature.com/articles/s41526-020-00130-8

Development of a human heart-on-a-chip model using induced pluripotent stem cells, fibroblasts and endothelial cells 査読

Liu Y, Wang M, Liang Y, Naruse K, Takahashi K

European Heart Journal 42 ( Supplement_11 ) 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Oxford University Press (OUP)

Abstract

Background

The use of animal models in cardiovascular research is associated with two serious, intrinsic problems: inaccuracy in the extrapolation of data obtained from animals such as rodents due to different cardiac physiology and animal ethics.

Purpose

To develop an artificial human heart model for cardiovascular research using organ-on-a-chip technology and human cells

Methods

Organ chips made of silicone (polydimethylsiloxane) that have two microfluidic channels, a top channel and a bottom channel, separated by a 50-μm thick membrane with 7-μm pores hexagonally packed at 40-μm intervals (Figure 1), were used in this study.

We seeded 10,000 human umbilical vein endothelial cells on the membrane surface in the bottom channel to mimic the vasculature. Next, we seeded a mixture of 100,000 human-induced pluripotent stem cells (hiPSCs) and 50,000 human gingival fibroblasts on the membrane surface in the top channel (Figure 1). Human gingival fibroblasts facilitate cardiac differentiation of hiPSCs [1]. We performed the cardiac differentiation of hiPSCs using a previously described protocol [1]. Culture medium was perfused at a constant rate of 60 μl/h to maintain the culture.

Results

We observed spontaneous contraction of hiPSC-derived cardiomyocytes 20–26 days after the start of the differentiation protocol. Simultaneously, we conducted live intracellular calcium imaging using a fluorogenic calcium-sensitive dye, Cal-520 AM (5 μM in the culture medium). hiPSC-derived cardiomyocytes exhibited a periodic, coordinated pattern of calcium influx synchronised with their contraction under fluorescence microscopy (Figure 2A). Moreover, we found that the β-adrenergic agonist noradrenaline elevated the heart rate of hiPSC-derived cardiomyocytes on the organ chips in a dose-dependent manner (Figures 2A, B).

After observing the contraction and intracellular calcium influx of hiPSC-derived cardiomyocytes, we performed immunocytochemistry. Confocal microscopy indicated that the fluorescent signal obtained from anti-cardiac troponin T antibody staining in the top channel exhibited a typical striated pattern with 1.56±0.12-μm interval that reflected sarcomere structure (Figure 2C, yellow). Moreover, the fluorescent signal obtained from anti-CD31 antibody staining in the bottom channel exhibited a typical pattern at the boundary between cells, which is expected at the cell–cell junction of endothelial cells.

Conclusion

We developed a human heart-on-a-chip model that was confirmed by the functional response to noradrenaline and the histological evidence of sarcomere structure and vasculature, with a capability of live imaging. We expect that this model would be useful for examining the physiological function and for the pharmacological analysis of not only the normal heart but also the heart that reflects specific patient's pathophysiology using patient-derived hiPSCs.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Japan Society for the Promotion of Science Figure 1Figure 2

DOI： 10.1093/eurheartj/ehab724.3190

Meta-Analysis-Assisted Detection of Gravity-Sensitive Genes in Human Vascular Endothelial Cells 査読

Yin Liang, Mengxue Wang, Yun Liu, Chen Wang, Ken Takahashi, Keiji Naruse

Frontiers in Cell and Developmental Biology 9 689662 2021年8月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Frontiers Media SA

Gravity affects the function and maintenance of organs, such as bones, muscles, and the heart. Several studies have used DNA microarrays to identify genes with altered expressions in response to gravity. However, it is technically challenging to combine the results from various microarray datasets because of their different data structures. We hypothesized that it is possible to identify common changes in gene expression from the DNA microarray datasets obtained under various conditions and methods. In this study, we grouped homologous genes to perform a meta-analysis of multiple vascular endothelial cell and skeletal muscle datasets. According to the t-distributed stochastic neighbor embedding (t-SNE) analysis, the changes in the gene expression pattern in vascular endothelial cells formed specific clusters. We also identified candidate genes in endothelial cells that responded to gravity. Further, we exposed human umbilical vein endothelial cells (HUVEC) to simulated microgravity (SMG) using a clinostat and measured the expression levels of the candidate genes. Gene expression analysis using qRT-PCR revealed that the expression level of the prostaglandin (PG) transporter gene <italic>SLCO2A1</italic> decreased in response to microgravity, consistent with the meta-analysis of microarray datasets. Furthermore, the direction of gravity affected the expression level of <italic>SLCO2A1</italic>, buttressing the finding that its expression was affected by gravity. These results suggest that a meta-analysis of DNA microarray datasets may help identify new target genes previously overlooked in individual microarray analyses.

DOI： 10.3389/fcell.2021.689662

Involvement of Transient Receptor Potential Vanilloid Channel 2 in the Induction of Lubricin and Suppression of Ectopic Endochondral Ossification in Mouse Articular Cartilage. 査読国際誌

Nakamoto H, Katanosaka Y, Chijimatsu R, Mori D, Xuan F, Yano F, Omata Y, Maenohara Y, Murahashi Y, Kawaguchi K, Yamagami R, Inui H, Taketomi S, Taniguchi Y, Kanagawa M, Naruse K, Tanaka S, Saito T

Arthritis & rheumatology (Hoboken, N.J.) 73 ( 8 ) 1441 - 1450 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: Transient receptor potential vanilloid channel 2 (TRPV2) is a Ca2+ -permeable channel and plays a role in mediating intracellular Ca2+ current via mechanical stimuli. This study was undertaken to examine the expression and role of TRPV2 in adult articular cartilage and the development of osteoarthritis (OA). METHODS: We examined TRPV2 expression in mouse and human articular cartilage. We analyzed the development of OA in Col2a1-CreERt2 ;Trpv2fl/fl mice and Trpv2fl/fl littermates in the resection of the medial meniscus and medial collateral ligament model (n = 5 each), the destabilization of the medial meniscus model (n = 5 each), and the aging mouse model (n = 8-9 each). We examined marker protein expression in these joints, Ca2+ influx by mechanical stimuli, and downstream pathways in vitro. RESULTS: TRPV2 was expressed in mouse and human articular cartilage and ectopic ossification lesions. In all mouse models of OA examined, Col2a1-CreERt2 ;Trpv2fl/fl mice were observed to have enhanced degradation of articular cartilage accompanied by decreased expression of lubricin/Prg4, and marked formation of periarticular ectopic ossification. Mechanical stress-induced Ca2+ influx was decreased by Trpv2 knockout (KO). Prg4 induction by fluid-flow shear stress was diminished in Trpv2-KO mouse chondrocytes, and this was mediated by the Ca2+ /calmodulin-dependent protein kinase kinase-cyclic AMP response element binding protein axis. Hypertrophic differentiation was enhanced in Trpv2-KO mouse chondrocytes. Increased activity of calcineurin and nuclear translocation of nuclear factor in activated T cells 1 induced by fluid-flow shear stress or TRP agonist treatment was reversed by Trpv2 knockout. CONCLUSION: Our findings demonstrate regulation of articular cartilage by TRPV2 through Prg4 induction and suppression of ectopic ossification.

DOI： 10.1002/art.41684

Role of the TRPM4 channel in mitochondrial function, calcium release, and ROS generation in oxidative stress 査読

Chen Wang, Jian Chen, Mengxue Wang, Keiji Naruse, Ken Takahashi

Biochemical and Biophysical Research Communications 566 190 - 196 2021年8月

Production of TRPM4 knockout cell line using rat cardiomyocyte H9c2 査読

Chen Wang, Masakazu Maeda, Jian Chen, Mengxue Wang, Keiji Naruse, Ken Takahashi

MethodsX 8 101404 - 101404 2021年5月

The Mechanisms of the Development of Atherosclerosis in Prediabetes 査読

Yin Liang, Mengxue Wang, Chen Wang, Yun Liu, Keiji Naruse, Ken Takahashi

International Journal of Molecular Sciences 22 ( 8 ) 4108 - 4108 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI AG

Lifestyle changes, such as overeating and underexercising, can increase the risk of prediabetes. Diabetes is one of the leading causes of atherosclerosis, and recently it became clear that the pathophysiology of atherosclerosis progresses even before the onset of diabetic symptoms. In addition to changes in platelets and leukocytes in the hyperglycemic state and damage to vascular endothelial cells, extracellular vesicles and microRNAs were found to be involved in the progression of prediabetes atherosclerosis. This review discusses the cellular and molecular mechanisms of these processes, with an intention to enable a comprehensive understanding of the pathophysiology of prediabetes and atherosclerosis.

DOI： 10.3390/ijms22084108

Systematic Understanding of Pathophysiological Mechanisms of Oxidative Stress-Related Conditions—Diabetes Mellitus, Cardiovascular Diseases, and Ischemia–Reperfusion Injury 査読

Wang M, Liu Y, Liang Y, Naruse K, Takahashi K

Frontiers in Cardiovascular Medicine 8 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Frontiers Media SA

Reactive oxygen species (ROS) plays a role in intracellular signal transduction under physiological conditions while also playing an essential role in diseases such as hypertension, ischemic heart disease, and diabetes, as well as in the process of aging. The influence of ROS has some influence on the frequent occurrence of cardiovascular diseases (CVD) in diabetic patients. In this review, we considered the pathophysiological relationship between diabetes and CVD from the perspective of ROS. In addition, considering organ damage due to ROS elevation during ischemia–reperfusion, we discussed heart and lung injuries. Furthermore, we have focused on the transient receptor potential (TRP) channels and L-type calcium channels as molecular targets for ROS in ROS-induced tissue damages and have discussed about the pathophysiological mechanism of the injury.

DOI： 10.3389/fcvm.2021.649785

Treatment of Oxidative Stress with Exosomes in Myocardial Ischemia 査読

Yun Liu, Mengxue Wang, Yin Liang, Chen Wang, Keiji Naruse, Ken Takahashi

International Journal of Molecular Sciences 22 ( 4 ) 1729 - 1729 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI AG

A thrombus in a coronary artery causes ischemia, which eventually leads to myocardial infarction (MI) if not removed. However, removal generates reactive oxygen species (ROS), which causes ischemia–reperfusion (I/R) injury that damages the tissue and exacerbates the resulting MI. The mechanism of I/R injury is currently extensively understood. However, supplementation of exogenous antioxidants is ineffective against oxidative stress (OS). Enhancing the ability of endogenous antioxidants may be a more effective way to treat OS, and exosomes may play a role as targeted carriers. Exosomes are nanosized vesicles wrapped in biofilms which contain various complex RNAs and proteins. They are important intermediate carriers of intercellular communication and material exchange. In recent years, diagnosis and treatment with exosomes in cardiovascular diseases have gained considerable attention. Herein, we review the new findings of exosomes in the regulation of OS in coronary heart disease, discuss the possibility of exosomes as carriers for the targeted regulation of endogenous ROS generation, and compare the advantages of exosome therapy with those of stem-cell therapy. Finally, we explore several miRNAs found in exosomes against OS.

DOI： 10.3390/ijms22041729

The inhibitory role of rab11b in osteoclastogenesis through triggering lysosome-induced degradation of c-Fms and RANK surface receptors. 査読

Tran MT, Okusha Y, Feng Y, Morimatsu M, Wei P, Sogawa C, Eguchi T, Kadowaki T, Sakai E, Okamura H, Naruse K, Tsukuba T, Okamoto K

Int J Mol Sci 21 ( 24 ) 9352 - 9352 2020年12月

In vitro Neo-Genesis of Tendon/Ligament-Like Tissue by Combination of Mohawk and a Three-Dimensional Cyclic Mechanical Stretch Culture System. 査読

Kataoka K, Kurimoto R, Tsutsumi H, Chiba T, ato T, Shishido K, Kato M, Ito Y, Cho Y, Hoshi O, Mimata A, Sakamaki Y, Nakamichi R, Lotz MK, Naruse K, Asahara H

Front Cell Dev Biol 8 2020年6月

Model of Ischemic Heart Disease and Video-Based Comparison of Cardiomyocyte Contraction Using hiPSC-Derived Cardiomyocytes. 査読

Liu Y, Liang Y, Wang M, Wang C, Wei H, Naruse K, Takahashi K

J Vis Exp 159 ( 159 ) e61104 2020年5月

Increased hydrostatic pressure induces nuclear translocation of DAF-16/FOXO in C. Elegans 査読国際誌

Watanabe N, Morimatsu M, Fujita A, Teranishi M, Sudevan S, Watanabe M, Iwasa H, Hata Y, Kagi H , Nishiyama M, Naruse K, Higashitani A

Biochem Biophys Res Commun 523 ( 4 ) 853 - 858 2020年3月

Elimination of fukutin reveals cellular and molecular pathomechanisms in muscular dystrophy-associated heart failure. 査読国際誌

Ujihara Y, Kanagawa M, Mohri S, Takatsu S, Kobayashi K, Toda T, Naruse K, Katanosaka Y

Nat Commun 10 ( 1 ) 5754 - 5754 2019年12月

Mechanical strain attenuates cytokine-induced ADAMTS9 expression via transient receptor potential vanilloid type 1. 査読国際誌

Exp Cell Res 383 ( 2 ) 111556 - 111556 2019年10月

Development of a model of ischemic heart disease using cardiomyocytes differentiated from human induced pluripotent stem cells. 査読

Wei H, Wang C, Guo R, Takahashi K, Naruse K

Biochemical and biophysical research communications 520 ( 3 ) 600 - 605 2019年10月

Spiral Trajectory Modulation of Rheotaxic Motile Human Sperm in Cylindrical Microfluidic Channels of Different Inner Diameters. 査読

Nishina S, Matsuura K, Naruse K

Acta medica Okayama 73 ( 3 ) 213 - 221 2019年6月

L-type calcium channel modulates mechanosensitivity of the cardiomyocyte cell line H9c2. 査読国際誌

Takahashi K, Hayashi S, Miyajima M, Omori M, Wang J, Kaihara K, Morimatsu M, Wang C, Chen J, Iribe G, Naruse K, Sokabe M

Cell Calcium 79 68 - 74 2019年5月

Cyclic stretch enhances reorientation and differentiation of 3-D culture model of human airway smooth muscle. 査読

Asano S, Ito S, Morosawa M, Furuya K, Naruse K, Sokabe M, Yamaguchi E, Hasegawa Y

Biochemistry and biophysics reports 16 32 - 38 2018年12月

TRPV2 is required for mechanical nociception and the stretch-evoked response of primary sensory neurons. 査読

Katanosaka K, Takatsu S, Mizumura K, Naruse K, Katanosaka Y

Scientific reports 8 ( 1 ) 16782 - 16782 2018年11月

Stretching of single DNA molecules caused by accelerating flow on a microchip. 査読

Hirano K, Iwaki T, Ishido T, Yoshikawa Y, Naruse K, Yoshikawa K

The Journal of chemical physics 149 ( 16 ) 165101 - 165101 2018年10月

Human gingival fibroblast feeder cells promote maturation of induced pluripotent stem cells into cardiomyocytes. 査読

Matsuda Y, Takahashi K, Kamioka H, Naruse K

Biochemical and biophysical research communications 503 ( 3 ) 1798 - 1804 2018年9月

Role of the TRPM4 Channel in Cardiovascular Physiology and Pathophysiology. 査読

Wang C, Naruse K, Takahashi K

Cells 7 ( 6 ) E62 - E62 2018年6月

TRPC3 participates in angiotensin II type 1 receptor-dependent stress-induced slow increase in intracellular Ca2+ concentration in mouse cardiomyocytes. 査読

Yamaguchi Y, Iribe G, Kaneko T, Takahashi K, Numaga-Tomita T, Nishida M, Birnbaumer L, Naruse K

The Journal of Physiological Sciences 68 ( 2 ) 153 - 164 2018年3月

Effects of Mechanical Stress on Periodontal Ligament 査読

Fujita Ayano, Morimatsu Masatoshi, Nishiyama Masayoshi, Takashiba Shogo, Naruse Keiji

BIOPHYSICAL JOURNAL 114 ( 3 ) 143A 2018年2月

The effects of load on transmural differences in contraction of isolated mouse ventricular cardiomyocytes. 査読

Khokhlova A, Iribe G, Katsnelson L, Naruse K, Solovyova O

J Mol Cell Cardiol 114 276 - 287 2018年1月

Mechano-sensitivity of mitochondrial function in mouse cardiac myocytes 査読

Iribe G, Kaihara K, Yamaguchi Y, Nakaya M, Inoue R and Naruse K

Progress in Biophysics and Molecular Biology, Progress in biophysics and biophysical chemistry 130 ( Pt B ) 315 - 322 2017年11月

Role of TRPC3 and TRPC6 channels in the myocardial response to stretch: Linking physiology and pathophysiology. 査読

Yamaguchi Y, Iribe G, Nishida M and Naruse K

Progress in Biophysics & Molecular Biology 130 ( Pt B ) 264 - 272 2017年11月

Effects of simulated ischemia on the transmural differences in the Frank-Starling relationship in isolated mouse ventricular cardiomyocytes 査読

Khokhlova A, Iribe G, Yamaguchi Y, Naruse K and Solovyova O

Progress in Biophysics and Molecular Biology, Progress in biophysics and biophysical chemistry 130 ( Pt B ) 323 - 332 2017年11月

Simultaneous mapping of multiple proteins in heart using matrix-assisted laser desorption/ionization imaging mass spectrometry 査読

Takahashi K, Naruse K

European Heart Journal 38 ( Suppl 1 ) ehx501.45 2017年8月

Effect of Oxidative Stress on Cardiovascular System in Response to Gravity 査読

Ken Takahashi, Hiroki Okumura, Rui Guo, Keiji Naruse

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 18 ( 7 ) 2017年7月

記述言語：英語出版者・発行元：MDPI AG

Long-term habitation in space leads to physiological alterations such as bone loss, muscle atrophy, and cardiovascular deconditioning. Two predominant factors-namely space radiation and microgravity-have a crucial impact on oxidative stress in living organisms. Oxidative stress is also involved in the aging process, and plays important roles in the development of cardiovascular diseases including hypertension, left ventricular hypertrophy, and myocardial infarction. Here, we discuss the effects of space radiation, microgravity, and a combination of these two factors on oxidative stress. Future research may facilitate safer living in space by reducing the adverse effects of oxidative stress.

DOI： 10.3390/ijms18071426

Imaging of Cell Mechanics under High Gravity by Rotational Microscope

Masatoshi Morimatsu, Ken Takahashi, Ayano Fujita, Keiji Naruse

BIOPHYSICAL JOURNAL 112 ( 3 ) 271A - 272A 2017年2月

Effects of bepridil on stretch-activated BKca channels and stretch-induced extrasystoles in isolated chick hearts. 査読

Jin H, Iribe G and Naruse K

Physiological Research 66 ( 3 ) 459 - 465 2017年

Dynamic Remodeling of the Heart and Blood Vessels: Implications of Health and Disease 査読

Ken Takahashi, Hulin Piao, Keiji Naruse

Mechanobiology: Exploitation for Medical Benefit 175 - 189 2016年11月

記述言語：英語掲載種別：論文集(書籍)内論文出版者・発行元：wiley

Long-term exposure to pressure/volume overload of the heart due to hypertension or aortic stenosis induces pathological hypertrophy and remodeling, and eventually causes heart failure. This process accompanies pathological phenomena such as inflammation, apoptosis, and arrhythmia. On the other hand, physical exercise promotes physiological hypertrophy and remodeling of the heart, thereby enhancing cardiac performance. Interestingly, recent research has suggested that enhancement of heart function is a result not only of physiological hypertrophy of pre-existing cardiomyocytes, but also of cardiac stem cell activation and myocyte formation. Furthermore, exercise improves exacerbated cardiac function in heart diseases, including dilated cardiomyopathy (DCM) and myocardial infarction (MI). The suggested mechanisms of action of exercise remedies for these diseases include angiogenesis, cardiac resynchronization, and inhibition of inflammatory cytokines. However, excessive exercise can cause arrhythmogenic remodeling and sudden death. In this chapter, we elaborate the mechanisms of hypertrophy and remodeling under physiological and pathological conditions and discuss future directions for coping with pathological hypertrophy and remodeling.

DOI： 10.1002/9781118966174.ch11

Induced NCX1 overexpression attenuates pressure overload-induced pathological cardiac remodelling 査読

Yoshihiro Ujihara,Keiichiro Iwasaki,Satomi Takatsu,Ken Hashimoto,Keiji Naruse*,Satoshi Mohri,Yuki Katanosaka*

Cardiovascular Research, Cardioscience 111 ( 4 ) 348 - 361 2016年9月

Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti-inflammation phenotypes and ameliorated diabetic polyneuropathy. 査読

Omi M, Hata M, Nakamura N, Miyabe M, Kobayashi Y, Kamiya H, Nakamura J, Ozawa S, Tanaka Y, Takebe J, Matsubara T, Naruse K

Journal of diabetes investigation 7 ( 4 ) 485 - 496 2016年7月

Innovation of vascular engineering by mechanomedicine 査読

Ken Takahashi, Keiji Naruse

Vascular Engineering: New Prospects of Vascular Medicine and Biology with a Multidiscipline Approach 283 - 296 2016年1月

記述言語：英語掲載種別：論文集(書籍)内論文出版者・発行元：Springer Japan

This article describes how physical forces contribute to development, physiology, and pathology of vascular cells, focusing on endothelial cells and vascular smooth muscle cells. Based on these basic understandings of the mechanobiology, we discuss mechanomedicine, an application of the mechanobiology to medicine. Basic knowledge about cellular responses, such as cellular signal transduction pathway, gene expression, and cytoskeletal remodeling, to mechanical stimuli is important for understanding the pathology of vascular diseases including atherosclerosis. Introducing the knowledge of the vascular mechanobiology will not only contribute to the development of regenerative medicine using pluripotent stem cells but also provide a way to prevent diseases caused by thromboembolisms, such as myocardial and cerebral infarctions.

DOI： 10.1007/978-4-431-54801-0_15

[Response to mechanical stimulus and cardiovascular homeostasis.] 査読

Takahashi K, Naruse K

Clin Calcium 26 ( 12 ) 1671 - 1676 2016年

Mechanical Stretch on Human Skin Equivalents Increases the Epidermal Thickness and Develops the Basement Membrane 査読

Tokuyama E, Nagai Y, Takahashi K, Naruse K

PLoS One 10 ( 1 ) e0141989 - e0141989 2015年11月

Transient receptor potential melastatin-4 is involved in hypoxia-reoxygenation injury in the cardiomyocytes. 査読

Piao H, Takahashi K, Yamaguchi Y, Wang C, Liu K, Naruse K

PLoS One 10 ( 4 ) e0121703 - e0121703 2015年4月

A simple method for decreasing the liquid junction potential in a flow-through-type differential pH sensor probe consisting of pH-FETs by exerting spatiotemporal control of the liquid junction. 査読

Yamada A, Mohri S, Nakamura M, Naruse K

Sensors (Basel) 15 ( 4 ) 7898 - 7912 2015年4月

Development of a Fluidic Gripper for Isolated Cardiomyocytes 査読

Yohei Yamaguchi, Yasuyo Yamaguchi, Shuichi Wakimoto, Gentaro Iribe, Keiji Naruse

Proc. of The 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society 110 - 110 2015年

Real-time imaging of ATP release induced by mechanical stretch in human airway smooth muscle cells. 査読

Takahara N, Ito S, Furuya K, Naruse K, Aso H, Kondo M, Sokabe M and Hasegawa Y

Am J Respir Cell Mol Biol 51 ( 6 ) 772 - 782 2014年12月

Ca2+ influx and ATP release mediated by mechanical stretch in human lung fibroblasts. 査読

Murata N, Ito S, Furuya K, Takahara N, Naruse K, Aso H, Kondo M, Sokabe M and Hasegawa Y

Biochem Biophys Res Commun 453 ( 1 ) 101 - 105 2014年10月

The significant role of Na⁺/Ca²⁺ exchanger 1 on local Ca²⁺ control beneath T-tubule membrane 査読

Ujihara Yoshihiro, Iwasaki Keiichiro, Takatsu Satomi, Hashimoto Ken, Naruse Keiji, Mohri Satoshi, Katanosaka Yuki

生体医工学 52 212 - O-213 2014年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Japanese Society for Medical and Biological Engineering

Na⁺/Ca²⁺ exchanger (NCX1) is essential Ca²⁺ regulator of myocyte Ca²⁺ homeostasis and specially localized at transverse tubules (T-tubules) membrane. T-tubules are invaginations of the sarcolemma and critical for myocyte contraction, especially as the main site of excitation-contraction coupling. Therefore, T-tubule disorganization is linked to decreased contractility in heart failure, but the molecular mechanism is not clear. We analyzed the alteration of T-tubule structure and Ca2+ handling during the progression of heart failure after transverse aortic constriction (TAC)-surgery, using cardiac-specific and inducible NCX1 transgenic mice. In progression of cardiac dysfunction, sarcoplasmic reticulum Ca²⁺ ATPase and NCX1 activity were down-regulated before T-tubule disorganization. The inducing NCX1 overexpression after TAC-surgery prevented T-tubule disorganization and contractile dysfunction under prolonged pressure-overload, with improvement of myocyte Ca²⁺ handling. These results suggest that local Ca²⁺ control beneath the T-tubule membrane is crucial for the maintenance of myocyte structure and function, in which NCX1 has a pivotal role.

DOI： 10.11239/jsmbe.52.O-212

Paper-based diagnostic devices for estimating human sperm motility 査読

Koji Matsuura, Wenqian Li, Kuan-Hung Chen, Yuka Asano, Keiji Naruse, Chao-Min Cheng

Transactions of Japanese Society for Medical and Biological Engineering 52 551 - O-552 2014年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Japan Soc. of Med. Electronics and Biol. Engineering

Low-cost paper-based diagnostic device for human sperm motility has developed to know sperm motility without consulting fertility clinics. We compared the signal pattern of the paper-based sperm motility assay using 4-channel pattern (cross) and 2-channel pattern (line) papers, and investigated difference in signal patterns using some tetrazorium salts for the assay. Using these two paper patterns, we can examine whether human sperm motility in semen is more than 50% or 0%. XTT and WST-8 reagents treated paper-based device can be used. We concluded that MTT treated line pattern paper is suitable for the purpose to reduce the cost of the device.

DOI： 10.11239/jsmbe.52.O-551

Effects of axial stretch on mitochondrial reactive oxygen species in cardiac myocytes 査読

Gentaro Iribe, Keiko Kaihara, Keiji Naruse

Transactions of Japanese Society for Medical and Biological Engineering 52 44 2014年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Japan Soc. of Med. Electronics and Biol. Engineering

Myocardium contracts against ventricular wall stretch that comes along with ventricular filling. Mitochondria generate required ATP for myocardial contraction. It is well known that mitochondrial ATP production process is one of the sources of reactive oxygen species (ROS). ROS are known as toxic molecules, but also important physiological regulators of intracellular signaling pathways. In the present study, we investigate the relation between myocardial stretch and mitochondrial ROS production, and discuss the role of mitochondria on myocardial response to stretch. Isolated mouse ventricular myocytes were exposed to 10% axial stretch using carbon fiber technique. ROS production was studied using DCF-loaded cells. Axial stretch significantly increased ROS production. Applying 5 μM mitochondrial metabolic uncoupler FCCP blunted the response, indicating mitochondrial ROS production is stretch-sensitive. The present results suggest that stretch enhances electron transport chain to prepare for the more ATP production for the more preloaded, namely, the more energy-consuming contraction.

DOI： 10.11239/jsmbe.52.SY-44

Load dependency in force-length relations in isolated single cardiomyocytes. 査読

Iribe G, Kaneko T, Yamaguchi Y, Naruse K

Prog Biophys Mol Biol. 115 ( 2-3 ) 103 - 114 2014年8月

Directed differentiation of patient-specific induced pluripotent stem cells identifies the transcriptional repression and epigenetic modification of NKX2-5, HAND1, and NOTCH1 in hypoplastic left heart syndrome. 査読

Kobayashi J, Yoshida M, Tarui S, Hirata M, Nagai Y, Kasahara S, Naruse K, Ito H, Sano S and Oh H

PLoS One 9 ( 7 ) e102796 - e102796 2014年7月

The neutral self-assembling peptide hydrogel SPG-178 as a topical hemostatic agent. 査読

Komatsua S, Nagai Y, Naruse K and Kimata Y

PLoS One 9 ( 7 ) e102778 - e102778 2014年7月

Paper-based diagnostic devices for evaluating the quality of human sperm. 査読

Matsuura, K, Chen KH, Tsai CH, Li W, Asano Y, Naruse K and Cheng CM

Microfluid Nanofluidics 16 ( 5 ) 857 - 867 2014年5月

TRPV2 is critical for the maintenance of cardiac structure and function in mice. 査読

Katanosaka Y, Iwasaki K, Ujihara Y, Takatsu S, Nishitsuji K, Kanagawa M, Sudo A, Toda T, Katanosaka K, Satoshi M and Naruse K

Nat Commun 5 ( 5 ) 3932 - 3932 2014年5月

蛍光ライブイメージングを用いた骨組織中における細胞内カルシウムオシレーションの計測

石原嘉人, 菅原康代, 上岡寛, 川邉紀章, 成瀬恵治, 山城隆

日本骨形態計測学会雑誌 24 ( 1 ) 15 - 22 2014年3月

記述言語：日本語出版者・発行元：日本骨形態計測学会

細胞内カルシウム(Ca2+)は多様な細胞機能を仲介する重要な情報伝達物質であり、Ca2+オシレーションと呼ばれる周期的なCa2+濃度の上昇様式は、骨代謝調節を含む広範な生理機構に関与すると考えられている。しかし、3次元的な骨芽細胞-骨細胞ネットワークから成り立つ骨組織中でのCa2+オシレーションの動態は、周囲の骨基質が障壁となるためこれまで不明であった。近年我々は、骨組織をまるごと生きた状態のままCa2+イメージングする事に成功し、骨芽細胞と骨細胞の自律性細胞内Ca2+オシレーションの存在と、それらの現象に対するメカニカルストレスの影響およびギャップ結合の関与について報告した。本論文では、蛍光ライブイメージングを用いた骨組織中のCa2+オシレーションについて最新の研究成果を交えて解説する。(著者抄録)

Oscillatory intracellular Ca²⁺responses in living bone 査読

Ishihara Y, Sugawara Y, Kamioka H, Kawanabe N, Naruse K, Yamashiro T

Journal of Oral Biosciences 56 ( 2 ) 49 - 53 2014年

Involvement of S1P1 receptor pathway in angiogenic effects of a novel adenosine-like nucleic acid analog COA-Cl in cultured human vascular endothelial cells. 査読国際誌

Igarashi J, Hashimoto T, Kubota Y, Shoji K, Maruyama T, Sakakibara N, Takuwa Y, Ujihara Y, Katanosaka Y, Mohri S, Naruse K, Yamashita T, Okamoto R, Hirano K, Kosaka H, Takata M, Konishi R, Tsukamoto I

Pharmacology Research & Perspectives 2 ( 5 ) e00068 - e00068 2014年

Coarse-grained molecular dynamics simulations of biomolecules 査読

Ken Takahashi, Takayuki Oda, Keiji Naruse

AIMS Biophysics 1 ( 1 ) 1 - 15 2014年

記述言語：英語出版者・発行元：American Institute of Mathematical Sciences

Coarse-grained molecular dynamics (CGMD) simulations are increasingly being used to analyze the behaviors of biological systems. When appropriately used, CGMD can simulate the behaviors of molecular systems several hundred times faster than elaborate all-atom molecular dynamics simulations with similar accuracy. CGMD parameters for lipids, proteins, nucleic acids, and some artificial substances such as carbon nanotubes have been suggested. Here we briefly discuss a method for CGMD system configuration and the types of analysis and perturbations that can be performed with CGMD simulations. We also describe specific examples to show how CGMD simulations have been applied to various situations, and then describe experimental results that were used to validate the simulation results. CGMD simulations are applicable to resolving problems for various biological systems.

DOI： 10.3934/biophy.2014.1.1

Effect of azelnidipine and amlodipine on single cell mechanics in mouse cardiomyocytes. 査読

Iribe G, Kaihara K, Ito H, Naruse K

Eur J Pharmacol 715 ( 1-3 ) 142 - 146 2013年9月

Impaired viability of muscle precursor cells in muscular dystrophy with glycosylation defects and amelioration of its severe phenotype by limited gene expression. 査読

Kanagawa M, Yu CC, Ito C, Fukada S, Hozoji-Inada M, Chiyo T, Kuga A, Matsuo M, Sato K, Yamaguchi M, Ito T, Ohtsuka Y, Katanosaka Y, Miyagoe-Suzuki Y, Naruse K, Kobayashi K, Okada T, Takeda S, Toda T

Hum Mol Genet 22 ( 15 ) 3003 - 3015 2013年8月

9-phenanthrol, a TRPM4 inhibitor, protects isolated rat hearts from ischemia-reperfusion injury 査読

Wang J, Takahashi K, Piao H, Qu P, Naruse K

PLOS ONE 8 ( 7 ) e70587 - e70587 2013年7月

Rac1 recruitment to the archipelago structure of the focal adhesion through the fluid membrane as revealed by single-molecule analysis. 査読

Shibata AC, Chen LH, Nagai R, Ishidate F, Chadda R, Miwa Y, Naruse K, Shirai YM, Fujiwara TK, Kusumi A

Cytoskeleton 70 ( 3 ) 161 - 177 2013年3月

Ex vivo real-time observation of Ca(2+) signaling in living bone in response to shear stress applied on the bone surface. 査読

Ishihara Y, Sugawara Y, Kamioka H, Kawanabe N, Hayano S, Balam TA, Naruse K, Yamashiro T

Bone 53 ( 1 ) 204 - 215 2013年3月

A tilting embryo culture system increases the number of high-grade human blastocysts with high-implantation competence. 査読

Hara T, Matsuura K, Kodama T, Sato K, Kikkawa Y, Muneto T, Tanaka J, Naruse K

Reprod Biomed Online 26 ( 3 ) 260 - 268 2013年3月

Mechanical stretch increases the proliferation while inhibiting the osteogenic differentiation in dental pulp stem cells. 査読

Hata M, Naruse K, Ozawa S, Kobayashi Y, Nakamura N, Kojima N, Omi M, Katanosaka Y, Nishikawa T, Naruse K, Tanaka Y, Matsubara T

Tissue Eng Part A 19 ( 5-6 ) 625 - 633 2013年3月

Detection of Micrococcus luteus biofilm formation in microfluidic environments by pH measurement using an ion-sensitive field-effect transistor. 査読

Matsuura K, Asano Y, Yamada A, Naruse K

Sensors 13 ( 2 ) 2484 - 2493 2013年2月

Mechanobiology in cardiac physiology and diseases. 査読

Takahashi K, Kakimoto Y, Toda K, Naruse K

J Cell Mol Med 17 ( 2 ) 225 - 232 2013年2月

Synthesis and slow-release characteristics of a self-assembling peptide gel containing phenylalanine azide. 査読

Matsuura K, Kitamatsu M, Nagai Y, Naruse K

Recent Patents on Nanomedicine 3 ( 2 ) 140 - 145 2013年

Developing a small, inexpensive planar patch-clamp device. 査読

Kuniyasu K, Fukasawa T, Takahashi K, Naruse K

Trans JSMBE 51 ( suppl ) R-14 2013年

Fabrication of a simple and compact patch clamp system for high-throughput recording. 査読

Takahashi K, Fukasawa T, Kuniyasu K, Naruse K

Trans JSMBE 51 ( suppl ) R-149 2013年

Stretch-activated BK channel and heart function. 査読

Takahashi K and Naruse K

Prog Biophys Mol Biol 110 ( 2-3 ) 239 - 244 2012年10月

Archipelago architecture of the focal adhesion: membrane molecules freely enter and exit from the focal adhesion zone. 査読

Shibata AC, Fujiwara TK, Chen L, Suzuki KG, Ishikawa Y, Nemoto YL, Miwa Y, Kalay Z, Chadda R, Naruse K and Kusumi A

Cytoskeleton 69 ( 6 ) 380 - 392 2012年6月

In situ imaging of the autonomous intracellular Ca(2+) oscillations of osteoblasts and osteocytes in bone. 査読

Ishihara Y, Sugawara Y, Kamioka H, Kawanabe N, Kurosaka H, Naruse K and Yamashiro T

Bone 50 ( 4 ) 842 - 852 2012年4月

The mechanical stimulation of cells in 3D culture within a self-assembling peptide hydrogel. 査読

Nagai Y, Yokoi H, Kaihara K and Naruse K

Biomaterials 33 ( 4 ) 1044 - 1051 2012年2月

Screening of sperm velocity by fluid mechanical characteristics of a cyclo-olefin polymer microfluidic sperm-sorting device. 査読

Matsuura K, Takenami M, Kuroda Y, Hyakutake T, Yanase S and Naruse K

Reprod Biomed Online 24 ( 1 ) 109 - 115 2012年1月

Development of observation system to investigate both intracellular calcium concentration and mechanical stimuli to mammalian embryos 査読

Koji Matsuura, Koyo Watanabe, Mieko Kodama, Yuka Kuroda, Keiji Naruse

2011 Int. Symp. on Micro-NanoMechatronics and Human Science, Symp. on "COE for Education and Research of Micro-Nano Mechatronics", Symposium on "Hyper Bio Assembler for 3D Cellular System Innovation" 99 - 104 2012年

記述言語：英語掲載種別：研究論文（国際会議プロシーディングス）

Using an air-actuating device, we investigated the cellular response to mechanical stimuli (MS) in mouse blastocysts. Both MS and intracellular calcium concentration ([Ca 2+] i) were quantified based on time-resolved confocal microscopy images in the polydimethylsiloxane (PDMS) microfluidic channels by deforming a 0.1-mm membrane. [Ca 2+] i was measured in a stained mouse embryo with Fluo-4 AM using confocal fluorescence microscopy. We captured a z-series stack of sections encompassing the entire embryo. When translocation velocities of the embryo and shear stress were 40 μm/s and 0.01 dyne/cm 2, respectively, a 10% increase in the sum of fluorescent intensities (FI) was observed. When blastocysts were compressed, FI also increased in response to the applied MS. Compressive force estimated from the shape of the blastocysts was approximately 0.5-2.0 μN according to a force deformation curve for the mouse embryo. The average FI and sum of FIs increased by a factor of 1.1-1.2 times compared with those observed before MS. The increase in the sum of FI indicated that enhancement of [Ca 2+] i would be induced by these MS. © 2011 IEEE.

DOI： 10.1109/MHS.2011.6102167

Role of sarcolemmal BK(Ca) channels in stretch-induced extrasystoles in isolated chick hearts. 査読

Iribe G, Jin H, Naruse K

Circulation Journal 75 ( 11 ) 2552 - 2558 2011年11月

Microtubule dynamics regulate cyclic stretch-induced cell alignment in human airway smooth muscle cells. 査読

Morioka M, Parameswaran H, Naruse K, Kondo M, Sokabe M, Hasegawa Y, Suki B, Ito S

PLoS ONE 6 ( 10 ) e26384 2011年10月

Comparison between loose fragment chondrocytes and condyle fibrochondrocytes in cellular proliferation and redifferentiation. 査読

Takata N, Furumatsu T, Abe N, Naruse K, Ozaki T

J Orthop Sci 16 ( 5 ) 589 - 597 2011年9月

Regulation of mechanical stress-induced MMP-13 and ADAMTS-5 expression by RUNX-2 transcriptional factor in SW1353 chondrocyte-like cells. 査読

Tetsunaga T, Nishida K, Furumatsu T, Naruse K, Hirohata S, Yoshida A, Saito T, Ozaki T

Osteoarthritis Cartilage 19 ( 2 ) 222 - 232 2011年2月

Glucose dependency of the metabolic pathway of HEK 293 cells measured by a flow-through type pH/CO2 sensor system using ISFETs. 査読

Yamada A, Mohri S, Nakamura M and Naruse K

IEEJ Transactions on Electronics, Informaiton and Systems 131 ( 9 ) 1535 - 1539 2011年

Ischemia-induced angiogenesis is impaired in aminopeptidase A deficient mice via down-regulation of HIF-1α. 査読

Kubota R, Numaguchi Y, Ishii M, Niwa M, Okumura K, Naruse K, Murohara T

Biochem Biophys Res Commun 402 ( 2 ) 396 - 401 2010年11月

In-vitro culture with a tilting device in chemically defined media during meiotic maturation and early development improves the quality of blastocysts derived from In-vitro matured and fertilized porcine oocytes. 査読

Koike T, Matsuura K, Naruse K, Funahashi H

J Reprod Dev 56 ( 5 ) 552 - 557 2010年10月

Application of a microfluidic sperm sorter to the in-vitro fertilization of porcine oocytes reduced the incidence of polyspermic penetration 査読

Sano H, Matsuura K, Naruse K, Funahashi H

Theriogenology 74 ( 5 ) 863 - 870 2010年9月

Blastocyst quality scoring based on morphologic grading correlates with cell number. 査読

Matsuura K, Hayashi N, Takiue C, Hirata R, Habara T, Naruse K

Fertil Steril 94 ( 3 ) 1135 - 1137 2010年8月

Actin cytoskeleton regulates stretch-activated Ca²⁺ influx in human pulmonary microvascular endothelial cells 査読

Ito S, Suki B, Kume H, Numaguchi Y, Ishii M, Iwaki M, Kondo M, Naruse K, Hasegawa Y, Sokabe M

Am J Respir Cell Mol Biol 43 ( 1 ) 26 - 34 2010年7月

Effects of axial stretch on sarcolemmal BKCa channels in post-hatch chick ventricular myocytes. 査読

Iribe G, Jin H, Kaihara K, Naruse K

Exp Physiol 95 ( 6 ) 699 - 711 2010年6月

Improved development of mouse and human embryos using a tilting embryo culture system. 査読

Matsuura K, Hayashi N, Kuroda Y, Takiue C, Hirata R, Takenami M, Aoi Y, Yoshioka N, Habara T, Mukaida T, Naruse K

Reprod Biomed Online 20 ( 3 ) 358 - 364 2010年3月

A fully automated pH measurement system for 96- well microplates using a semiconductor-based pH sensor 査読

Yamada A, Mohri S, Nakamura M, Naruse K

Sensors & Actuators: B. Chemical 143 ( 2 ) 464 - 469 2010年1月

Automatic measurement system for biological applications based on pH using ISFET sensor probe 査読

Akira Yamada, Satoshi Mohri, Michihiro Nakamura, Keiji Naruse

2010 International Symposium on Micro-NanoMechatronics and Human Science: From Micro and Nano Scale Systems to Robotics and Mechatronics Systems, MHS 2010, Micro-Nano GCOE 2010, Bio-Manipulation 2010 19 - 24 2010年

記述言語：英語掲載種別：研究論文（国際会議プロシーディングス）

Throughput in the cell response analysis is expected to progress in medicine and biology. In this paper, we construct a method for the measurement of cell activity that is measured by the pH fluctuation of the solution around the cell. To improve throughput of the measurements, first we constructed an automatic pH measurement system using ion-sensitive field-effect transistor (ISFET), and the system composed of 96-well microplate, pump, XYZ stage, and PC. The basic data of the cell activity was taken from human embryonic kidney 293 (HEK 293) cells by the use of flow-through type measuring chamber. ©2010 IEEE.

DOI： 10.1109/MHS.2010.5669583

Application of mechanical stimuli using a microfluidic air actuating system to cultured mammalian embryos 査読

Jing-Chun Li, Koji Matsuura, Yuka Kuroda, Hiroaki Funahashi, Keiji Naruse

2010 International Symposium on Micro-NanoMechatronics and Human Science: From Micro and Nano Scale Systems to Robotics and Mechatronics Systems, MHS 2010, Micro-Nano GCOE 2010, Bio-Manipulation 2010 29 - 34 2010年

記述言語：英語掲載種別：研究論文（国際会議プロシーディングス）

Mammalian embryos experience not only hormonal but also mechanical stimuli, such as shear stress, compression, and friction force, in the fallopian tube before nidation. We aim to develop a novel and simple system to apply mechanical stimuli (MS) similar to those generated inside the oviduct to cultured mammalian embryos. Possible MS include shear stress (SS) caused by fluid dynamics and compression of embryos due to interactions with the wall of the oviduct. A new culture system was developed to increase SS and to apply MS during in vitro embryo cultures. We developed an air actuating system with microfluidic channels to apply MS by deforming a 0.1-mm-thick poly(dimethylsiloxiane) membrane and evaluated MS applied to ICR mouse embryos inside the microfluidic channel. Using this air actuating system, we applied compression to mouse embryos inside the medium channel and estimated SS on the basis of the velocity of the embryos' motion. By changing the syringe velocity, we applied different types of MS to the em bryos. These results suggested that multiple MS such as SS and compression can be applied at the same time. MS applied using this system was similar to those generated in the physiological environment of the oviduct. ©2010 IEEE.

DOI： 10.1109/MHS.2010.5669581

Optimizing the conditions for pH measurement with an automated pH measurement system using a flow-through-type differential sensor probe consisting of pH-FETs. 査読

Yamada A, Mohri S, Nakamura M, Naruse K

Journal of Robotics and Mechatronics 22 ( 2 ) 197 - 203 2010年

A rapid microfluidic perfusion system for analysis at the single cellular level 査読

Yamada A, Katanosaka Y, Mohri S, Naruse K

IEEE TRANS NanoBioscience 8 ( 4 ) 306 - 311 2009年12月

Mechanical stretch enhances IL-8 production in pulmonary microvascular endothelial cells 査読

Iwaki M, Ito S, Morioka M, Iwata S, Numaguchi Y, Ishii M, Kondo M, Kume H, Naruse K, Sokabe M, Hasegawa Y

Biochem Biophys Res Commun 389 ( 3 ) 531 - 536 2009年11月

Mesenchymal stem cell-based gene therapy with prostacyclin synthase enhanced neovascularization in hindlimb ischemia. 査読

Ishii M, Numaguchi Y, Okumura K, Kubota R, Ma X, Murakami R, Naruse K, Murohara T

Atherosclerosis 206 ( 1 ) 109 - 118 2009年9月

Mechanical stretch stimulates integrin alphaVbeta3-mediated collagen expression in human anterior cruciate ligament cells. 査読

Tetsunaga T, Furumatsu T, Abe N, Nishida K, Naruse K, Ozaki T

J Biomech 42 ( 13 ) 2097 - 2103 2009年9月

Stress-Axis Regulated Exon (STREX) in the C terminus of BK(Ca) channels is responsible for the stretch sensitivity. 査読

Naruse K, Tang QY, Sokabe M

Biochem Biophys Res Commun 385 ( 4 ) 634 - 639 2009年8月

The TRPV4 cation channel mediates stretch-evoked Ca2+ influx and ATP release in primary urothelial cell cultures. 査読

Mochizuki T, Sokabe T, Araki I, Fujishita K, Shibasaki K, Uchida K, Naruse K, Koizumi S, Takeda M, Tominaga M

J Biol Chem 284 ( 32 ) 21257 - 21264 2009年8月

Application of a numerical simulation to improve the separation efficiency of a sperm sorter 査読

Hyakutake T, Hashimoto Y, Yanase S, Matsuura K, Naruse K

Biomed Microdevices 11 ( 1 ) 25 - 33 2009年2月

Uniaxial cyclic stretch increases glucose uptake into C2C12 myotubes through a signaling pathway independent of insulin-like growth factor I. 査読

Iwata M, Suzuki S, Hayakawa K, Inoue T and Naruse K

Horm Metab Res 41 ( 1 ) 16 - 22 2009年1月

Fabricating small-scale, curved, polymeric structures with convex and concave menisci through interfacial free energy equilibrium 査読

Cheng CM, Matsuura K, Wang IJ, Kuroda Y, Leduc PR, Naruse K

Lab Chip 9 ( 22 ) 3306 - 3309 2009年

Impairment of leukocyte deformability in patients undergoing esophagectomy 査読

Suemori T, Morimatsu H, Mizobuchi S, Morita K, Katanosaka Y, Mohri S, Naruse K

Clin Hemorheol Microcirc 41 ( 2 ) 127 - 136 2009年

Application of a flow-through type pH/CO2 sensor system based on ISFET for evaluation of the glucose dependency of the metabolic pathways in cultured cells 査読

Satoshi Mohri, Akira Yamada, Noriko Goda, Michihiro Nakamura, Keiji Naruse, Fumihiko Kajiya

SENSORS AND ACTUATORS B-CHEMICAL 134 ( 2 ) 447 - 450 2008年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE SA

We have previously reported that a flow-through type pH/CO2 sensor system using two ion sensitive field effect transistors (ISFETs) could be utilized to evaluate the production rate of total carbonate (secreted CO2 + secreted bicarbonate ion) and free lactic acid (secreted lactic acid -secreted bicarbonate ion). To validate the usefulness of this system, we applied it to the quantitative analysis of metabolic switching by the change Of glucose concentrations in cultured bovine arterial endothelium cell, human umbilical vein endothelium cell and rat cardiac muscle cell. In all of these cell species, a decrease of glucose concentration increased total carbonate that represents the cellular respiration activity and decreased free lactic acid that represents glycolysis activity. We firstly analyzed a switching of metabolic pathways from glycolysis to respiration with a decrease of glucose quantitatively. This ISFET system can be applicable to many biological investigations by analyzing metabolic activity and give dynamic cellular information. (C) 2008 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.snb.2008.05.021

Examination of signalling pathways involved in muscarinic responses in bovine ciliary muscle using YM-254890, an inhibitor of the Gq/11 protein. 査読

Yasui F, Miyazu M, Yoshida A, *Naruse K and Takai A

Br J Pharmacol 154 ( 4 ) 890 - 900 2008年6月

A novel Ca2+ influx pathway activated by mechanical stretch in human airway smooth muscle cells. 査読

Ito S, Kume H, *Naruse K, Kondo M, Takeda N, Iwata S, Hasegawa Y and Sokabe M

Am J Respir Cell Mol Biol 38 ( 4 ) 407 - 413 2008年4月

Cyclic strain induces mouse embryonic stem cell differentiation into vascular smooth muscle cells by activating PDGF receptor β 査読

Shimizu N, Yamamoto K, Obi S, Kumagaya S, Masumura T, Shimano Y, Naruse K, Yamashita JK, Igarashi T, Ando J

J Appl Physiol 104 ( 3 ) 766 - 772 2008年3月

Effects of tensile and compressive strains on response of a chondrocytic cell line embedded in type I collagen gel. 査読

Hirano Y, Ishiguro N, Sokabe M, Takigawa M and *Naruse K

J Biotechnol 133 ( 2 ) 245 - 252 2008年1月

Analysis of cyclic-stretching responses using cell-adhesion-patterned cells. 査読

Katanosaka Y, Bao JH,Komatsu T, Suemori T, Yamada A, Mohri S and *Naruse K

J Biotechnol 133 ( 1 ) 82 - 89 2008年1月

Impaired NO-mediated vasodilation with increased superoxide but robust EDHF function in right ventricular arterial microvessels of pulmonary hypertensive rats. 査読

Kajiya M, Hirota M, Inai Y, Kiyooka T, Morimoto T, Iwasaki T, Endo K, Mohri S, Shimizu J, Yada T, Ogasawara Y, *Naruse K, Ohe T and Kajiya F

Am J Physiol 292 ( 6 ) H2737 - H2744 2007年6月

Automation of pH measurement using a flow-through type differential pH sensor system based on pH-FET 査読

Mohri S, Nakamura M, Naruse K

IEEJ Trans SM 127 ( 8 ) 367 - 370 2007年

記述言語：英語出版者・発行元：The Institute of Electrical Engineers of Japan

Automatic pH measurement system was developed by using a flow-through type differential pH-FET sensor. The system was operated by repeating 60 sec cycle consisting of 36 sec of washing period, 4 sec of moving period, and 20 sec of measuring period. In washing period, the differential pH-FET sensor was washed with baseline solution. In measuring period, about 50 μl of sample solution was withdrawn to the space around a measurement pH-FET, and the change of differential source potential was measured. Absolute values of error for nine sample solutions with weak buffering ability were less than 0.146 pH, and were 0.071 pH in average. From this experiment, it was suggested that high-speed and automated pH measurement will be possible by using pH-FET sensors even for sample solutions of weak buffer ability.

DOI： 10.1541/ieejsmas.127.367

その他リンク： https://jlc.jst.go.jp/DN/JALC/00298152597?from=CiNii

Uniaxial cyclic stretch-stimulated glucose transport is mediated by a ca-dependent mechanism in cultured skeletal muscle cells. 査読

Iwata M, Hayakawa K, Murakami T, *Naruse K, Kawakami K, Inoue-Miyazu M, Yuge L and Suzuki S

Pathobiology 74 ( 3 ) 159 - 168 2007年

Roles of stretch-activated cation channel and Rho-kinase in the spontaneous contraction of airway smooth muscle. 査読

Ito S, Kume H, Oguma T, Ito Y, Kondo M, Shimokata K, Suki B and *Naruse K

Eur J Pharmacol 552 ( 1-3 ) 135 - 142 2006年12月

Viscoelastic and dynamic nonlinear properties of airway smooth muscle tissue--roles of mechanical force and the cytoskeleton--. 査読

Ito S, Majumdar A, Kume H, Shimokata K, Naruse K, Lutchen KR, Stamenovic D and Suki B*

Am J Physiol 290 ( 6 ) L1227 - L1237 2006年6月

Bi-phasic activation of eNOS in response to uni-axial cyclic stretch is mediated by differential mechanisms in BAECs. 査読

Takeda H, Komori K, Nishikimi N, Nimura Y, Sokabe M and *Naruse K

Life Sci 79 ( 3 ) 233 - 239 2006年6月

Spatial and temporal application of microfluidics to cells. 査読

Yamada A, katanosaka Y, Mohri S and *Naruse K

Proc. of 2006 International Symposium on Micro-Nanomechatronics and Human Science 220 - + 2006年

Activation of a mechanosensitive BK channel by membrane stress created with amphipaths. 査読

Qi Z, Chi S, Su X, *Naruse K and Sokabe M

Mol Membr Biol 22 ( 6 ) 519 - 527 2005年11月

Involvement of reactive oxygen species in cyclic stretch-induced NF-jB activation in human fibroblast cells. 査読

Amma H, *Naruse K,Ishiguro N and Sokabe M

Brit J Pharmacol 145 ( 3 ) 364 - 373 2005年6月

Mechanotransduction by integrin is essential for IL-6 secretion from endothelial cells in response to uniaxial continuous stretch. 査読

Sasamoto A, Nagino M, Kobayashi S, *Naruse K, Nimura Y and Sokabe M

Am J Physiol 288 ( 5 ) C1012 - C1022 2005年5月

Fabrication of reconfigurable protein matrices by cracking. 査読

Zhu X, Mills KL, Peters PR, Bahng JH, Liu EH, Shim J, *Naruse K, Csete ME, Thouless MD and Takayama S

Nature Materials 4 ( 5 ) 403 - 406 2005年5月

Stretch-induced cell proliferation is mediated by FAK-MAPK pathway. 査読

Wang JG, Miyazu M, Sokabe M and *Naruse K

Life Sci 76 ( 24 ) 2817 - 2825 2005年4月

Reconfigurable protein matrices for prolonged neuroblasts patterning and retraction 査読

XY Zhu, KL Mills, PR Peters, K Naruse, ME Csete, MD Thouless, S Takayama

2005 3rd IEEE/EMBS Special Topic Conference on Microtechnology in Medicine and Biology 393 - 395 2005年

記述言語：英語掲載種別：研究論文（国際会議プロシーディングス）出版者・発行元：IEEE

Here we present long-term patterning and response studies of neuroblasts on arrays of extracellular matrix (ECM) protein lines fabricated by cracking a polymer-supported thin film and selectively depositing proteins inside the cracks. Neuroblasts cultured for five days on the protein matrix switched between spreading and retraction upon changing the protein line width. This technique provides a novel tool to pursue further understanding of the basic mechanisms of neuroblast pathfinding on adhesion and morphology. Biomedical device design will also benefit from materials engineered with the reconfigurable protein patterns.

Catheter-based prostacyclin synthase gene transfer prevents in-stent restenosis in rabbit atheromatous arteries. 査読

Numaguchi, S., Okumura, K., Harada, M., *Naruse, K., Yamada, M., Osanai, H., Matsui, H., Ito, M., Murohara, T.

Cardiovasc. Res. 61 ( 1 ) 177 - 185 2004年1月

Characterization of a Functionally Expressed Stretch-Activated BKca channel cloned from Chick Ventricular Myocytes. 査読

Tang, Q.Y., Qi, Z., *Naruse, K., Sokabe, M.

J. Membr. Biology 196 ( 3 ) 185 - 200 2003年12月

Stretch-induced IL-6 secretion from endothelial cells requires NF-kappaB activation. 査読

Kobayashi, S., Nagino, M., Komatsu, S., *Naruse, K., Nimura, Y., Nakanishi, M., Sokabe, M.

Biochem. Biophys. Res. Com. 308 ( 2 ) 306 - 312 2003年8月

Selective Chemical Treatment of Cellular Microdomains Using Multiple Laminar Streams. 査読

Takayama, S., Ostuni, E., LeDuc, P., *Naruse, K., Ingber, D.E., Whitesides, G.M.

Chemistry and Biology 10 ( 2 ) 123 - 130 2003年2月

The role of calcium in regulating the response of osteoblasts to mechanical stretch 査読

Danceu T, Adam R, Naruse K, Freeman M, Hauschka P

FEBS letter 536 193 - 197 2003年

Mechanical stress-dependent secretion of interleukin 6 by endothelial cells after portal vein embolization: clinical and experimental studies. 査読

Kawai, M., *Naruse, K., Komatsu, S., Kobayashi, S., Nagino, M., Nimura, Y., Sokabe, M.

J. Hepatol. 37 ( 2 ) 240 - 246 2002年8月

Prostacyclin synthase gene transfer modulates cyclooxygenase-2-derived prostanoid synthesis and inhibits neointimal formation in rat balloon-injured arteries. 査読

Yamada, M., Numaguchi, Y., Okumura, K., Harada, M., *Naruse, K., Matsui, H., Ito, T., Hayakawa, T.

Arterioscler Thromb. Vasc. Biol. 22 ( 2 ) 256 - 262 2002年2月

Uni-axial cyclic stretch induces the activation of transcription factor nuclear factor kappaB in human fibroblast cells. 査読

Inoh, H., Ishiguro, N., Sawazaki, S., Amma, H., Miyazu, M., Iwata, H., Sokabe, M., *Naruse, K.

FASEB J. 16 ( 1 ) 405 - + 2002年1月

Protamine augments stretch induced calcium increase in vascular endothelium 査読

K Murase, K Naruse, A Kimura, K Okumura, T Hayakawa, M Sokabe

BRITISH JOURNAL OF PHARMACOLOGY 134 ( 7 ) 1403 - 1410 2001年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

1 Human umbilical vein endothelial cells cultured on a transparent silicone chamber were subjected to a short stretch pulse (ca. 1 s, 5-25% stretch) of their substrate and following increases in intracellular Ca2+ concentration ([Ca2+](i)) were measured by fluorescence intensity ratiometry using fura-2.
2 In response to mechanical stretch, the cells in HEPES buffered saline exhibited a Ca2+ transient in a dose dependent way. The response was completely dependent on external Ca2+ and inhibited by gadolinium (Gd3+), suggesting that it was mediated by the activation of a stretch activated cation channel (SACatC).
3 Interestingly, the stretch induced Ca2+ transient was significantly augmented in the presence of basic polypeptide, protamine. This augmented Ca2+ response was inhibited neither by Gd3+ nor by the deprivation of external Ca2+, indicating that the SACatC is not responsible for this phenomenon.
4 In contrast, this augmentation was inhibited by depletion of intracellular Ca2+ stores with thapsigargin or by the pretreatment with phospholipase inhibitors such as U73122 and manoalide.
5 These results suggest the presence of a metabotropic mechanoreceptor distinct from the SACatC in vascular endothelium. This augmented [Ca2+](i) increase may contribute to the vasodilating response induced by protamine during heparin neutralization in cardiac surgery.

DOI： 10.1038/sj.bjp.0704386

Uniaxial cyclic stretch induces focal adhesion kinase (FAK) tyrosine phosphorylation followed by mitogen-activated protein kinase (MAPK) activation 査読

JG Wang, M Miyazu, E Matsushita, M Sokabe, K Naruse

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 288 ( 2 ) 356 - 361 2001年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE

We investigated the role of tyrosine phosphorylation of FAK in the stretch-induced MAPKs (extracellular signal-regulated kinase (ERK), p38MAPK) activation in mutant FAK-transfected fibroblasts. In response to uniaxial cyclic stretch (1 Hz, 120% in length), the levels of tyrosine phosphorylation of the Tyr-397 and Tyr-925 of FAK in control cells increased and peaked at 5 min (2.75 +/- 0.51, n = 3), and 20 min (2.98 +/- 0.58, n = 3), respectively, and the activities of MAPKs increased and peaked at approximately 10 min. On the other hand, in the mutant FAK-transfected cells, the stretch-induced MAPKs activation was significantly inhibited. The stretch-induced activation of MAPKs was also significantly abolished by either treatment with Gd3+ or extracellular Ca2+ removal which may inhibit intracellular Ca2+ increase caused by the activation of cation selective (Ca2+-permeable) stretch activated (SACatC) channels. These results suggest that the stretch-induced tyrosine-phosphorylation of FAK via SACatC activation is critical for the stretch-induced MAPKs activation. (C) 2001 Academic Press.

DOI： 10.1006/bbrc.2001.5775

SA channel mediates superoxide production in HUVECs 査読

K Aikawa, N Nishikimi, T Sakurai, Y Nimura, M Sokabe, K Naruse

LIFE SCIENCES 69 ( 15 ) 1717 - 1724 2001年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

Superoxide production in response to cyclic stretch (1 Hz, 20 % in length) was investigated in human umbilical vein endothelial cells (HUVECs). The basal production of superoxide without stretch increased gradually, while the production of superoxide with stretch increased significantly as compared to that without stretch and it became significant 80 min after the onset of cyclic stretch (P<0.05, n=8-14). The superoxide production increased in a stretch-dependent manner and became significant when stretch was more than 10 % (p<0.05, n= 11-16). To investigate the involvement of SA channel, we added Gd3+ or EGTA in the reaction solution and examined the stretch-induced superoxide production. In cells stretched in the presence of 20 muM Gd3+, the stretch-induced superoxide production was significantly inhibited (at 120 min, p<0.05, n=8-18). The cyclic stretch-induced superoxide production was also significantly inhibited by the removal of extracellular Ca2+ with 5 mM EGTA (at 120 min, p<0.05, n = 8-18). Neither the application of Gd3+ nor the removal of extracellular Ca2+ significantly changed the basal production of superoxide. These data suggest that the stretch-induced superoxide production increases in time- and stretch-dependent manner and that the stretch-induced superoxide production in HUVECs is regulated by Ca2+ influx through SA channels. (C) 2001 Elsevier Science Inc. All rights reserved.

DOI： 10.1016/S0024-3205(01)01256-5

Mechanical behavior in living cells consistent with the tensegrity model 査読

N Wang, K Naruse, D Stamenovic, JJ Fredberg, SM Mijailovich, IM Toric-Norrelykke, T Polte, R Mannix, DE Ingber

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 98 ( 14 ) 7765 - 7770 2001年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：NATL ACAD SCIENCES

Alternative models of cell mechanics depict the living cell as a simple mechanical continuum, porous filament gel, tensed cortical membrane, or tensegrity network that maintains a stabilizing prestress through incorporation of discrete structural elements that bear compression. Real-time microscopic analysis of cells containing GFP-labeled microtubules and associated mitochondria revealed that living cells behave like discrete structures composed of an interconnected network of actin microfilaments and microtubules when mechanical stresses are applied to cell surface integrin receptors, Quantitation of cell tractional forces and cellular prestress by using traction force microscopy confirmed that microtubules bear compression and are responsible for a significant portion of the cytoskeletal prestress that determines cell shape stability under conditions in which myosin light chain phosphorylation and intracellular calcium remained unchanged. Quantitative measurements of both static and dynamic mechanical behaviors in cells also were consistent with specific a priori predictions of the tensegrity model. These findings suggest that tensegrity represents a unified model of cell mechanics that may help to explain how mechanical behaviors emerge through collective interactions among different cytoskeletal filaments and extracellular adhesions in living cells.

DOI： 10.1073/pnas.141199598

Subcellular positioning of small molecules 査読

Takayama S, Ostuni E, LeDuc P, Naruse K, Ingber DE, Whitesides GM

Nature 411 ( 6841 ) 1016 - 1016 2001年6月

Stretch-induced morphological changes of human endothelial cells depend on the intracellular level of Ca2+ rather than of cAMP 査読

T Yamada, K Naruse, M Sokabe

LIFE SCIENCES 67 ( 21 ) 2605 - 2613 2000年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

When exposed to a uni-axial cyclic stretch, cultured human umbilical vein endothelial cells (HUVECs) align and elongate perpendicular to the stretch axis. Previous studies showed that forskolin inhibited stretch-induced orientation of endothelial cells, suggesting that adenosine3:5-cyclic monophosphate (cAMP) plays an important role in the shape change. However, we have recently shown that stretch-induced shape changes in cultured HUVECs are due to increased [Ca2+],. In the present study, we examined the possible role of cAMP in stretch-induced shape changes in cultured HUVECs, Application of uni-axial cyclic stretch induced a gradual rise in cAMP reaching a peak level at 60 min after the onset of stretch. The adenylate cyclase activator, forskolin, increased the basal level of cAMP but inhibited the rise in [Ca2+](i) resulting in no cell shape changes. In contrast, N 6,2-dibutyryladenosine3:5-cyclic monophosphate (dbcAMP) enhanced the stretch-induced increase in cAMP and [Ca2+] and resulted in cell shape changes. On the other hand, 2'5'-dideoxyadenosine (DDA), an adenylate cyclase inhibitor, inhibited stretch-induced increases in cAMP and [Ca2+]i resulting in no cell shape changes. In summary, our data showed that cell shape changes were consistently dependent on [Ca2+](i) rather than cAMP levels. We conclude that the primary second messenger in the stretch-induced shape changes in HUVECs is intracellular Ca2+ rather than cAMP. (C) 2000 Elsevier Science Inc. All rights reserved.

DOI： 10.1016/S0024-3205(00)00844-4

Aldose reductase inhibition prevents glucose-induced apoptosis in cultured bovine retinal microvascular pericytes 査読

K Naruse, J Nakamura, Y Hamada, M Nakayama, S Chaya, T Komori, K Kato, Y Kasuya, K Miwa, K Naruse, N Hotta

EXPERIMENTAL EYE RESEARCH 71 ( 3 ) 309 - 315 2000年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ACADEMIC PRESS LTD

The pathogenesis of pericyte loss, an initial deficit in the early stage of diabetic retinopathy, remains unclear. Polyol pathway hyperactivity has been implicated in the pathogenesis of diabetic retinopathy, and recent studies have suggested that apoptosis may be involved in pericyte loss. The present study was conducted to investigate whether high glucose induces apoptosis in cultured bovine retinal pericytes. The effect of an aldose reductase inhibitor. SNK-860, was also examined. After a 5 day incubation with various concentrations of glucose (5.5-40 mM) in the presence or absence of SNK-860, the cell viability and the percentages of dead cells were measured. and staining with the TUNEL method and Hoechst 33342, and DNA electrophoresis were performed. High glucose reduced the viability and increased the percentages of dead cells. TUNEL-positive cells were observed in pericytes under high glucose, but not in those under 5.5 mM glucose. In the staining of nuclei with Hoechst 33342, the percentage of apoptotic cells in total cells counted under high glucose was higher than that under 5.5 mM glucose. DNA electrophoresis of pericytes cultured with high glucose demonstrated a 'ladder pattern'. Hyperosmolarity also induced apoptosis in pericytes, but less than that by high glucose. SNK-860 inhibited the glucose-induced apoptosis in pericytes. These observations suggest that the pericyte loss in diabetic retinopathy involves an apoptotic process, and that the polyol pathway hyperactivity plays an important role in inducing apoptosis in pericytes by high glucose. (C) 2000 Academic Press.

DOI： 10.1006/exer.2000.0882

Erratum: 'Molecular identification of a eukaryotic, stretch-activated nonselective cation channel' (Science (Aug. 6, 1999) (882)) 査読

M. Kanzaki, M. Nagasawa, I. Kojima, C. Sato, K. Naruse, M. Sokabe, H. Iida

Science 288 ( 5470 ) 1347 2000年5月

Molecular identification of a eukaryotic, stretch-activated nonselective cation channel 査読

M Kanzaki, M Nagasawa, Kojima, I, C Sato, K Naruse, M Sokabe, H Iida

SCIENCE 285 ( 5429 ) 882 - 886 1999年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER ASSOC ADVANCEMENT SCIENCE

Calcium-permeable, stretch-activated nonselective cation (SA Cat) channels mediate cellular responses to mechanical stimuli. However, genes encoding such channels have not been identified in eukaryotes. The yeast MID1 gene product (Mid1) is required for calcium influx in the yeast Saccharomyces cerevisiae. Functional expression of Midi in Chinese hamster ovary cells conferred sensitivity to mechanical stress that resulted in increases in both calcium conductance and the concentration of cytosolic free calcium. These increases were dependent on the presence of extracellular calcium and were reduced by gadolinium, a blocker of SA Cat channels. Single-channel analyses with cell-attached patches revealed that Midi acts as a calcium-permeable, cation-selective stretch-activated channel with a conductance of 32 picosiemens at 150 millimolar cesium chloride in the pipette. Thus, Midi appears to be a eukaryotic, SA Cat channel.

DOI： 10.1126/science.285.5429.882

An aldose reductase inhibitor prevents the glucose-induced increase in PDGF-beta receptor in cultured rat aortic smooth muscle cells 査読

Y Kasuya, J Nakamura, Y Hamada, M Nakayama, H Sasaki, T Komori, S Chaya, G Watanabe, K Naruse, E Nakashima, K Kato, N Hotta

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 261 ( 3 ) 853 - 858 1999年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ACADEMIC PRESS INC

To examine the role of platelet-derived growth factor (PDGF) and the polyol pathway in the growth activity of smooth muscle cells (SMCs), [H-3]-thymidine incorporation, [I-125]-PDGF-BB binding and expression of PDGF-beta receptor protein were measured in rat aortic SMCs cultured with 5.5 or 20 mM glucose with or without anti-PDGF antibody or an aldose reductase inhibitor, epalrestat. SMCs cultured with 20 mM glucose demonstrated an accelerated thymidine incorporation compared with SMCs cultured with 5.5 mM glucose, which was prevented by anti-PDGF antibody. This acceleration of growth activity by 20 mM: glucose was accompanied by an increase in PDGF-BB binding, which was due to the increased number of PDGF-beta receptors and the overexpression of PDGF-beta receptor protein. Epalrestat prevented all these abnormalities. These observations suggest that polyol pathway hyperactivity plays an important role in the proliferation of SMCs which may be mediated through the accelerated expression of PDGF-beta receptor protein. (C) 1999 Academic Press.

Characterization of a newly found stretch-activated K-Ca,K-ATP channel in cultured chick ventricular myocytes 査読

T Kawakubo, K Naruse, T Matsubara, N Hotta, M Sokabe

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 276 ( 6 ) H1827 - H1838 1999年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER PHYSIOLOGICAL SOC

With the use of the patch-clamp technique, five kinds of stretch-activated (SA) ion channels were identified on the basis of their single-channel conductances and ion selectivities in cultured chick ventricular myocytes. Because a high-conductance K+-selective channel predominated among these channels, we concentrated on characterizing its properties mostly using excised inside-out patches. With 145 mM KCl solution in the pipette and the bath, the channel had a conductance of 199.8 +/- 8.2 pS (n = 22). The ion selectivities among K+, Na+, Ca2+, and Cl- as estimated from their permeability ratios were P-Na/P-K = 0.03, P-Ca/P-K = 0.025, and P-Cl/P-K = 0.026. The probability of the channel being open (P-0) increased with the Ca2+ concentration in the bath ([Ca2+](b); dissociation constant Kd = 0.51 mu M at +30 mV) and membrane potential (voltage at half-maximal P-o, = 39.4 mV at 0.35 FIM [Ca2+](b)). The channel was blocked by gadolinium, tetraethylammonium, and charybdotoxin from the extracellular surface and, consequently, was identified as a Ca2+-activated K+ (K-Ca) channel type. The channel was also reversibly activated by ATP applied to the intracellular surface (K-d = 0.74 mM at 0.10 mu M [Ca2+](b) at + 30 mV). From these data taken together, we concluded that the channel is a new type of K-Ca channel that could be designated as an "SA K-Ca,K-ATP channel. "To our knowledge, this is the first report of K-Ca channel in heart cells.

Activation of pp60(src) is critical for stretch-induced orienting response in fibroblasts 査読

XR Sai, K Naruse, M Sokabe

JOURNAL OF CELL SCIENCE 112 ( 9 ) 1365 - 1373 1999年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：COMPANY OF BIOLOGISTS LTD

When subjected to uni-axial cyclic stretch (120% in length, 1 Hz), fibroblasts (3Y1) aligned perpendicular to the stretch axis in a couple of hours. Concomitantly with this orienting response, protein tyrosine phosphorylation of cellular proteins (molecular masses of approximately 70 kDa and 120-130 kDa) increased and peaked at 30 minutes, Immuno-precipitation experiments revealed that paxillin, pp125(FAK), and pp130(CAS) were included in the 70 kDa, and 120-130 kDa bands, respectively. Treatment of the cells with herbimycin A, a tyrosine kinase inhibitor, suppressed the stretch induced tyrosine phosphorylation and the orienting response suggesting that certain tyrosine kinases are activated by stretch. We focused on pp60(src), the most abundant tyrosine kinase in fibroblasts. The kinase activity of pp60(src) increased and peaked at 20 minutes after the onset of cyclic stretch. Treatment of the cells with an antisense S-oligodeoxynucleotide (S-ODN) against pp60(src), but not the sense S-ODN, inhibited the stretch induced tyrosine phosphorylation and the orienting response. To further confirm the involvement of pp60(src), we performed the same sets of experiments using c-src-transformed 3Y1 (c-src-3Y1) fibroblasts. Cyclic stretch induced a similar orienting response in c-src-3Y1 to that in wild-type 3Y1, but with a significantly faster rate. The time course of the stretch-induced tyrosine phosphorylation was also much faster in c-src-3Y1. than in 3Y1 fibroblasts, These results strongly suggest that cyclic stretch induces the activation of pp60(src) and that pp60(src) is indispensable for the tyrosine phosphorylation of pp130(CAS), pp125(FAK) and paxillin followed by the orienting response in 3Y1 fibroblasts.

Appropriately spaced nuclear localizing signals are necessary for efficient nuclear import of nonnuclear proteins 査読

HJW Borgeld, K Naruse, S Nishikawa, J Zhang, A Kikuchi, K Furukawa, K Yagi, M Tanaka

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 256 ( 2 ) 278 - 283 1999年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ACADEMIC PRESS INC

To deliver nonnuclear proteins into the nucleus, we have examined the locations and number of nuclear localizing signals by use of simian virus 40 large T-antigen (SV40Ta) and yeast enhanced green fluorescent protein (yEGFP) in Saccharomyces cerevisiae as a model system. When only one SV40Ta was added to either the N- or C-terminus of yEGFP, the fluorescence of yEGFP was detected in both the nucleus and the cytoplasm. When two SV40Ta signals were added, one to the N-terminus and one to the C-terminus of yEGFP (SV40Ta-yEGFP-SV40Ta), the fluorescence of yEGFP was localized in only the nucleus. When the presequence of cytochrome oxidase subunit IV (pCOXIV) was inserted between the SV40Ta and the N-terminus of yEGFP (SV40Ta-pCOXIV-yEGFP-SV40Ta) in this construct, the fluorescence was located in both the nucleus and the cytoplasm, suggesting that the increased distance between the two SV40Ta signals decreased the efficiency of transport into the nucleus. When an additional SV40Ta signal was inserted between pCOXIV and yEGFP (SV40Ta-pCOXIV-SV49Ta-yEGFP), the fluorescence was localized only in the nucleus, indicating that two SV40Ta signals spaced by pCOXIV of 28 amino acid residues forming an alpha-helix are potent in transporting yEGFP into the nucleus. These results indicate that two SV40Ta signals spaced appropriately are essential for the efficient transport of the nonnuclear protein into the nucleus. (C) 1999 Academic Press.

DOI： 10.1006/bbrc.1999.0269

Prostacyclin synthase gene transfer accelerates reendothelialization and inhibits neointimal formation in rat carotid arteries after balloon injury 査読

Y Numaguchi, K Naruse, M Harada, H Osanai, S Mokuno, K Murase, H Matsui, Y Toki, T Ito, K Okumura, T Hayakawa

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 19 ( 3 ) 727 - 733 1999年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

Prostacyclin (PGI(2)), a metabolite of arachidonic acid, has the vasoprotective effects of vasodilation, anti-platelet aggregation, and inhibition of smooth muscle cell proliferation. We hypothesized that an overexpression of endogenous PGI(2) may accelerate the recovery from endothelial damage and inhibit neointimal formation in the injured artery. To test this hypothesis, we investigated in vivo transfer of the PGI(2) synthase (PCS) gene into balloon-injured rat carotid arteries by a nonviral lipotransfection method. Seven days after transfection, a significant regeneration of endothelium was observed in the arteries transfected with a plasmid carrying the rat PCS gene (pCMV-PCS), but little regeneration was seen in those with the control plasmid carrying the lacZ gene (pCMV-lacZ) (percent luminal circumference lined by newly regenerated endothelium: 87.1+/-6.9% in pCMV-PCS-transfected vessels and 6.9+/-0.2% in pCMV-lacZ vessels, P<0.001). BrdU staining of arterial segments demonstrated a significantly lower incorporation in pCMV-PCS-transfected vessels (7.5+/-0.3% positive nuclei in vessel cells) than in pCMV-lacZ (50.7+/-9.6%, P<0.01). Moreover, 2 weeks after transfection, the PCS gene transfer resulted in a significant inhibition of neointimal formation (88% reduction in ratio of intima/media areas), whereas medial area was similar among the groups. Arterial segments transfected with pCMV-PCS produced significantly higher levels of 6-keto-PGF(1 alpha), the main metabolite of PGI(2), compared with the segments transfected with pCMV-lacZ (10.2+/-0.55 and 2.1+/-0.32 ng/mg tissue for pCMV-PCS and pCMV-placZ, P<0.001). In conclusion, this study demonstrated that an in vivo PCS gene transfer increased the production of PGI(2) and markedly inhibited neointimal formation with accelerated reendothelialization in rat carotid arteries after balloon injury.

Orientation change of cardiocytes induced by cyclic stretch stimulation: Time dependency and involvement of protein kinases 査読

K Kada, K Yasui, K Naruse, K Kamiya, Kodama, I, J Toyama

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 31 ( 1 ) 247 - 259 1999年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD

Mechanical stress has been implicated as one of the growth regulators in the heart. We investigated the effect of cyclic stretch stimulation on morphology and orientation of cultured cardiocytes. Embryonic rat (17 days postcoital) cardiomyocytes cultured on silicone dishes were cyclically stretched to 120% in length at a frequency of 30 cycles/min. After 12 h, in the initial stage of cultivation, cardiocytes and intracellular myofibrils oriented parallel to the stretch direction. When the stretch stimulus was prolonged to 24-48 h, myofibrils that oriented perpendicular to the stretch direction emerged. Furthermore. when the cells were stretched only in the later stage (after 24 h of cultivation). both cells and myofibrils tended to orient perpendicular to the stretch direction. Next we examined the effects of chemical compounds on these phase related changes in myofibril orientation None of the drugs tested (H-7, HA-1004, staurosporine, herbimycin A, genistein, GdCl3, and EGTA) blocked the parallel orientation of myofibrils induced by the initial-stage stretch. By contrast, H-7, staurosporine, herbimycin A, and genistein did inhibit almost completely the perpendicular orientation of the myofibrils induced by the late-stage stretch, but HA-1004, GdCl3, or EGTA did not, Immunoblotting study using anti-phsophotyrosine antibody indicated that tyrosine phosphorylation of a protein of about 125 kDa was enhanced in a time-dependent manner by the late-stage stretch, but not by the initial-stage stretch. In conclusion: the alignment change induced by cyclic stretch depends on the stage of cultivation: with stretch in the initial stage (within 12 h), cells and myofibrils orient parallel to the stretch; with stretch in the later stage (after 24 h), they orient perpendicular to the stretch. The effect of stretch in the later stage is likely mediated by protein kinase C and tyrosine kinase pathways. (C) 1999 Academic Press.

DOI： 10.1006/jmcc.1998.0865

An aldose redutase inhibitor prevents the intimal thickening in coronary arteries of galactose-fed beagle dogs 査読

Y. Kasuya, M. Ito, J. Nakamura, Y. Hamada, M. Nakayama, S. Chaya, T. Komori, K. Naruse, E. Nakashima, K. Kato, N. Koh, N. Hotta

Diabetologia 42 ( 12 ) 1404 - 1409 1999年

記述言語：英語掲載種別：研究論文（学術雑誌）

Aims/hypothesis. Although increased polyol pathway activity has been implicated in the pathogenesis of diabetic microangiopathy, the relation with diabetic macroangiopathy remains unclear. Galactose feeding is known to stimulate the polyol pathway and to develop abnormalites similar to those in diabetic microangiopathy. Our study was conducted to investigate whether an activation of polyol pathway by long-term treatment with galactose produced morphological changes in coronary arteries of dogs and the effect of an aldose reductase inhibitor, epalrestat, was also studied. Methods. Dogs received either normal chow or chow containing 30% galactose with or without epalrestat given orally (20 or 50 mg · kg-1). After 44 months, morphometric analyses of coronary arteries were carried out and the galactitol contents in aortas were measured. Results. The ratio of areas of the intimal layer to those of the medial layer, an indicator of intimal thickening, was statistically significantly increased in galactose-fed dogs compared with control dogs. Galactose-fed dogs had a remarkable accumulation of galactitol in their aortas. These morphological and biochemical deficits were reduced by treatment with epalrestat. Conclusion/interpretation. This report morphologically shows diabetes-like macrovascular abnormalities in galactosaemic animals, suggesting that polvol pathway hyperactivity is closely related to the development of diabetic macroangiopathy, which could be prevented by aldose reductase inhibition.

DOI： 10.1007/s001250051310

Uni-axial cyclic stretch induces c-src activation and translocation in human endothelial cells via SA channel activation 査読

K Naruse, Sai, X, N Yokoyama, M Sokabe

FEBS LETTERS 441 ( 1 ) 111 - 115 1998年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

The kinase activity of c-src increased and peaked at 15 min after an application of uni-axial cyclic stretch in HUVECs followed by a translocation of c-src to Triton-insoluble fraction. Suppression of c-src by an antisense S-oligodeoxynucleotide inhibited the stretch-induced tyrosine phosphorylation and morphological changes. The stretch-induced increase in c-src activity was inhibited by FK506, a specific inhibitor for calcineurin, by Gd3+, a blocker for stretch activated channels, and by the extracellular Ca2+ depletion suggesting the involvement of SA channels. These results strongly suggest c-src plays an important role in the downstream of SA channel activation followed by the morphological changes. (C) 1998 Federation of European Biochemical Societies.

DOI： 10.1016/S0014-5793(98)01528-2

Peroxide production and apoptosis in cultured cells carrying mtDNA mutation causing encephalomyopathy 査読

J Zhang, M Yoneda, K Naruse, HJW Borgeld, JS Gong, S Obata, M Tanaka, K Yagi

BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL 46 ( 1 ) 71 - 79 1998年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ACADEMIC PRESS AUST

When cybrids with a point mutation, which locates in the tRNA(Leu(UUR)) gene of mtDNA and causes a mitochondrial encephalomyopathy (MELAS syndrome), were exposed to a high concentration of oxygen (95%), the peroxide production markedly increased by 6 h of oxygen exposure, whereas the peroxide production was similar among the cybrids under a normal concentration of oxygen. The peroxide production by oxygen exposure was enhanced particularly in cybrids with high proportions of the mutant mtDNA and low respiratory capacities. The appearance of apoptotic cells by oxygen exposure was high in cybrids with the impaired respiratory function due to the mutation. An antioxidant NAC successfully suppressed both the peroxide production and apoptosis. These results imply that the peroxide production plays an important role in inducing apoptosis in :ells carrying; the mtDNA mutation causing encephalomyopathy.

Pp125(FAK) is required for stretch dependent morphological response of endothelial cells 査読

K Naruse, T Yamada, XR Sai, M Hamaguchi, M Sokabe

ONCOGENE 17 ( 4 ) 455 - 463 1998年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：NATURE PUBLISHING GROUP

In this study, critical signaling pathway required for the stretch induced morphological changes of human umbilical endothelial cells (HUVECs) was investigated. Uniaxial cyclic stretch (1 Hz, 20% in length) of the cells cultured on an elastic silicon membrane induced a gradual morphological change in the cells from a polygonal shape to an elongated spindle-like shape whose long axis was aligned perpendicular to the stretch axis, We found that protein tyrosine phosphorylation of cellular proteins increased and peaked at 20 min in response to cyclic stretch. Either treatment of cells with gadolinium (Gd3+), a potent blocker for stretch-activated channels, or removal of extracellular Ca2+ blocked the tyrosine phosphorylation of the proteins, suggesting that stretch-activated (SA) ion channels regulated stretch specific tyrosine phosphorylation, The major phosphorylated proteins had molecular masses of approximately 120-135 kDa, and 70 kDa, Immunoprecipitation experiments revealed that paxillin, focal adhesion kinase (pp125(FAK)) and pp130(CAS) were included in the 70 kDa and 120-135 kDa bands, respectively, The morphological change was inhibited by herbimycin A and genistein, inhibitors of tyrosine kinases, suggesting that tyrosine phosphorylation was required for the morphological change, In addition, the kinase activation of pp125(FAK) was observed in response to cyclic stretch, Moreover, suppression of pp125(FAK) expression by the antisense phosphorothioate oligodeoxynucleotides (S-ODN) in HUVECs resulted in inhibition of tyrosine phosphorylation of paxillin and the stretch-dependent morphological changes. These results suggest that an activation of tyrosine kinase(s) by an increase in intracellular Ca2+ and pp125(FAK) play a critical role in the unique morphological change specifically observed in endothelial cells subjected to uni-axial cyclic stretch.

DOI： 10.1038/sj.onc.1201950

Involvement of SA channels of cultured endothelial cells 査読

Keiji Naruse, Takako Yamada, Masahiro Sokabe

American Journal of Physiology - Heart and Circulatory Physiology 274 ( 5 ) H1532 - H1538 1998年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

The present work was designed to elucidate the involvement of Ca2+permeable stretch-activated (SA) channels in the orienting response of endothelial cells to uniaxial cyclic stretch. Endothelial cells from human umbilical vein were cultured on an elastic silicone membrane and subjected to uniaxial cyclic stretch (120% in length, 1 Hz). The cells started to change their morphology 15 min after the onset of stretch, and &gt
90% of the cells oriented perpendicularly to the stretch axis after 2 h. Associated with the orienting response, cell elongation proceeded with a slower rate. Both of the orientating and elongating responses were largely inhibited by the removal of external Ca2+ or by Gd3+, a potent blocker for the SA channel, but not by nifedipine. Intracellular Ca2+ concentration ([Ca2+](i)) transiently increased in response to uniaxial stretch, and the basal [Ca2+](i) gradually increased during cyclic stretch. This Ca2+ response was inhibited by the removal of extracellular Ca2+ or by the addition of Gd3+. These results suggest that stretch-dependent Ca2+ influx through SA channels is essential in the stretch-dependent cell orientation and elongation.

Involvement of SA channels in orienting response of cultured endothelial cells to cyclic stretch 査読

K Naruse, T Yamada, M Sokabe

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 274 ( 5 ) H1532 - H1538 1998年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER PHYSIOLOGICAL SOC

The present work was designed to elucidate the involvement of Ca2+-permeable stretch-activated (SA) channels in the orienting response of endothelial cells to uniaxial cyclic stretch. Endothelial cells from human umbilical vein were cultured on an elastic silicons membrane and subjected to uniaxial cyclic stretch (120% in length, 1 Hz). The cells started to change their morphology 15 min after the onset of stretch, and >90% of the cells oriented perpendicularly to the stretch axis after 2 h. Associated with the orienting response, cell elongation proceeded with a slower rate. Both of the orientating and elongating responses were largely inhibited by the removal of external Ca2+ or by Gd3+, a potent blocker for the SA channel, but not by nifedipine. Intracellular Ca2+ concentration ([Ca2+](i)) transiently increased in response to uniaxial stretch, and the basal [Ca2+](i) gradually increased during cyclic stretch. This Ca2+ response was inhibited by the removal of extracellular Ca2+ or by the addition of Gd3+. These results suggest that stretch-dependent Ca2+ influx through SA channels is essential in the stretch-dependent cell orientation and elongation.

Up-regulation of COX2 expression by uni-axial cyclic stretch in human lung fibroblast cells 査読

T Kato, N Ishiguro, H Iwata, T Kojima, T Ito, K Naruse

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 244 ( 3 ) 615 - 619 1998年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE

The effect of uni-axial cyclic mechanical stretch on the expression of cyclooxygenases (COX) was investigated in a human lung fibroblast cell line (TIG-1). In response to uni-axial cyclic stretch, the level of COX2 mRNA significantly increased and peaked at 3 h (9.09 +/- 3.82-fold, mean +/- standard error, n = 6, compared with that at 1 h). The level of the expression of COX2 protein peaked at 6 h, whereas the level of COX1 protein was not significantly changed. The involvement of stretch-activated (SA) channel was investigated in the stretch-induced COX2 production. The application of Gd3+, a blocker for SA channel, or the removal of extracellular Ca2+ inhibited the production of COX2 mRNA without any effect on the production of COX1 or GAPDH mRNA. These data strongly suggest that COX2 expression is up-regulated by uni-axial cyclic stretch via the activation of SA channel in human lung fibroblasts. (C) 1998 Academic Press.

DOI： 10.1006/bbrc.1998.8335

Both focal adhesion kinase and c-ras are required for the enhanced matrix metalloproteinase 9 secretion by fibronectin in ovarian cancer cells 査読

K Shibata, F Kikkawa, A Nawa, AA Thant, K Naruse, S Mizutani, M Hamaguchi

CANCER RESEARCH 58 ( 5 ) 900 - 903 1998年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER ASSOC CANCER RESEARCH

Cell adhesion to the extracellular matrix appears to trigger a cascade of intracellular signalings. We have shown previously that treatment of ovarian cancer cells with peritoneal conditioned medium or purified fibronectin (FN) activated matrix metalloproteinase 9 secretion and, thereby, cancer cell invasion, By use of antisense oligonucleotides to focal adhesion kinase (FAK) and a dominant-negative mutant of ras (S17Nras), we found that both FAK and c-Ras were required for the activation of matrix metalloproteinase 9 secretion by FN. In addition, both antisense oligonucleotides to FAR and S17Nras inhibited mitogen-activated protein kinase activation hy FN treatment, suggesting the involvement of mitogen-activated protein kinase in the FN-dependent signaling.

Bystander tumoricidal effect and gap junctional communication in lung cancer cell lines 査読

K Imaizumi, Y Hasegawa, T Kawabe, N Emi, H Saito, K Naruse, K Shimokata

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY 18 ( 2 ) 205 - 212 1998年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER LUNG ASSOC

Tumor cells expressing the herpes simplex virus-thymidine kinase (HSV-tk) gene become sensitive to ganciclovir (GCV), and the phenomenon by which tumor cells surrounding the HSV-tk expressing cells also become sensitive to CCV is known as the "bystander effect." The purpose of this study was to investigate the bystander effect in human lung-cancer cell lines, and the role of gap-junctional intercellular communication as the mechanism responsible for it. Gap-junctional intercellular communication was measured both with a dye-transfer assay involving single-cell microinjection of Lucifer Yellow and with a PKH26/calcein-AM double-dye-transfer assay. Significant bystander tumoricidal effect was observed in lung-cancer cell lines when cultured cells contained only 10% HSV-tk expressing cells. This was also observed to occur with cell lines of different origin or from different species. Although gap-junctional intercellular communication characterized by rapid transfer of Lucifer Yellow was not observed, we did detect gap-junctional communication marked by the slow transfer of calcein-AM in lung-cancer cell lines. However, neither an inhibitor (I-octanol) nor an enhancer (all trans-retinoic acid [ATRA]) of gap-junctional communication affected the extent of the bystander effect. These findings suggest that low levels of gap-junctional communication may be efficient for producing the bystander effect in lung-cancer cells, or chat other mechanisms may underlie this effect. Although gap-junctional communication may play an important role in generating the bystander effect in tumor cells expressing the HSV-tk gene, further knowledge of the mechanism of this effect may help improve the treatment of lung cancer with an HSV-tk system.

Up-regulation of integrin beta(3) expression by cyclic stretch in human umbilical endothelial cells 査読

N Suzuki, K Naruse, Y Asano, T Okamoto, N Nishikimi, T Sakurai, Y Nimura, M Sokabe

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 239 ( 2 ) 372 - 376 1997年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS

The effect of uni-axial cyclic mechanical stretch on the expression of the adhesion protein integrin was investigated. Human umbilical endothelial cells (HUVECs) cultured an fibronectin coated silicon membranes were subjected to uni-axial cyclic stretch, The level of expression of integrin beta(3) mRNA was found to be increased and peaked at 4 hours in response to cyclic stretch using a semiquantitative RT-PCR method. The increased level of the integrin mRNA from stretched HUVECs remained higher than that ii om non-stretched controls. The amount of integrin beta(3) also increased and peaked at 12 hr, Immuno-fluorescent microscopy revealed that the amount of integrin beta(3) adhesions increased in stretched HUVECs compared with that in non-stretched HUVECs. These results suggest that uni-axial cyclic stretch up-regulates the expression of integrin beta(3). This increase in integrin beta(3), may enhance the adhesiveness to the substratum and contribute to the protection of HUVECs against being peeled off from the vessel wall. (C) 1997 Academic Press.

DOI： 10.1006/bbrc.1997.7364

Mechanotransduction and intracellular signaling mechanisms of stretch-induced remodeling in endothelial cells 査読

M Sokabe, K Naruse, S Sai, T Yamada, K Kawakami, M Inoue, K Murase, M Miyazu

HEART AND VESSELS ( Suppl 12 ) 191 - 193 1997年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER

We investigated the signaling mechanism of stretch-induced cell remodeling in human umbilical vein endothelial cells (HUVECs). Freshly dissociated HUVECs were cultured on an elastic silicon membrane and subjected to uniaxial cyclic stretch (20% in length, 1Hz). The cells started to change their morphology as early as 15 min after stretch onset, and most cells eventually aligned perpendicularly to the stretch axis within Ih. This remodeling was dependent on the increase in intracellular calcium concentration ([Ca2+](i)) via a Ca2+-permeable stretch-activated (SA) channel. During the process of remodeling, extensive rearrangement of stress fibers and focal adhesions was observed, which may be close to the final step in the intracellular signaling cascade. This event was [Ca2+](i)-dependent, suggesting the existence of a Ca2+-dependent intermediate cascade that links [Ca2+](i) to the rearrangement of cytoskeletons and focal adhesions. We found that some proteins, including pp125(FAK) (focal adhesion kinase) and paxillin, were tyrosine phosphorylated during cyclic stretch in a Ca2+-dependent manner. Inhibition of this tyrosine phosphorylation prohibited the stretch-dependent rearrangement of cytoskeletons and focal adhesions as well as the remodeling. Finally the tyrosine kinase src, which could phosphorylate pp125(FAK), was found to be activated in a [Ca2+](i)-dependent way during stretch. All of the above molecular events were consistently Ca2+-dependent, which led us to propose the signaling cascade: SA channel activation --> [Ca2+](i) increase --> src activation --> protein tyrosine phosphorylation --> rearrangement of cytoskeletons and focal adhesions --> cell remodeling.

Mechanosensitive ion channels: single channel vs. whole cell activities 査読

Sokabe M, Naruse K, Nunogaki K

Prog Cell Res 6 139 - 149 1997年

Effects of repetitive stretch stimulation on neonatal rat cardiocytes in vitro 査読

Kada K, Yasui K, Naruse K, Toyama J

Environmental Medicine 40 ( 1 ) 69 - 72 1996年

Inhibitory action of repeated stretch stimulation on apoptosis in neonatal rat cardiocytes 査読

Yasui K, Shimano H, Kada K, Naruse K, Toyama J

Environmental Medicine 40 ( 2 ) 175 - 177 1996年

PLATEAU PATTERN OF AFFERENT DISCHARGE RATE FROM FROG-MUSCLE SPINDLES 査読

M SOKABE, K NUNOGAKI, K NARUSE, H SOGA, N FUJITSUKA, A YOSHIMURA, F ITO

JOURNAL OF NEUROPHYSIOLOGY 70 ( 1 ) 275 - 283 1993年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER PHYSIOLOGICAL SOC

1. A characteristic plateau pattern was observed in the rate of afferent discharges during ramp-and-hold stretch of spindles isolated from semitendinosus muscles of frogs. The plateau pattern was more frequent in summer frogs (84%) than winter frogs (11%).
2. The plateau pattern consisted of a discharge rate around 120 imp/s at the end of dynamic stretch, followed by second and third steps of plateau rates around 60 and 40 imp/s, respectively. The intervals of impulses in lower steps were approximately n times those of the top step.
3. The plateau pattern was not sensitive to cutting extracapsular myelinated branches or lowering temperature from 23 to 12-degrees-C. However, the number of the plateau was reduced in both cases.
4. Application of depolarizing current to the sensory terminal abolished the plateau pattern. In contrast, in spindles that did not show a plateau pattern, hyperpolarizing current induced such a pattern.
5. Calcium channel blockers and protein kinase C inhibitors abolished the plateau pattern. The plateau pattern could be established in quiescent spindles by drugs eliciting Ca2+ entry, raising cytosolic-free Ca2+, and activating protein kinase C.
6. The most striking aspect of the present study is the stability in the discharge rate at each step of the plateau, irrespective of different experimental conditions. This suggests that the spindle sensory terminal possesses a stable intrinsic rhythm generator in excitation, of which maximum frequency is 120 imp/s. The generator seems to be triggered by stretch stimulus and to be regulated by cytoplasmic Ca2+ and protein kinase C.

INVOLVEMENT OF STRETCH-ACTIVATED ION CHANNELS IN CA-2+ MOBILIZATION TO MECHANICAL STRETCH IN ENDOTHELIAL-CELLS 査読

K NARUSE, M SOKABE

AMERICAN JOURNAL OF PHYSIOLOGY 264 ( 4 ) C1037 - C1044 1993年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER PHYSIOLOGICAL SOC

Endothelial cells are subjected to shear stresses by blood flow, normal stresses by blood pressure, and stretch by vessel expansion. These forces are known to induce secretions of several vasoactive substances probably via internal calcium mobilization (R. F. Furchgott. Circ. Res. 53: 557-573, 1983; M. J. Peach, A. L. Loeb, H. A. Singer, and J. Saye. Hypertension Dallas 7, Suppl. I: I-94-1-100, 1985.). Here we report that stretching cellular membranes increased intracellular Ca2+ concentration ([Ca2+]i) in human umbilical endothelial cells cultured on silicon membranes. Upon application of a stretch pulse (3-s duration), [Ca2+]i increased rapidly and decayed slowly. The following results suggest that this increase arises from Ca2+ entry through stretch-activated (SA) channels: 1) the Ca2+ response disappeared when extracellular Ca2+ was removed; 2) gadolinium (Gd3+), a blocker for cation-selective SA channels, blocked the response but nifedipine did not; and 3) externally applied Mn2+, which is known to permeate mechanosensitive channels but not Ca2+ channels, entered the intracellular space immediately after an application of mechanical stretch. The increase in [Ca2+]i was found to consist of at least two components: an initial fast component and a delayed slower component. Ryanodine inhibited the slow component. It is suggested that stretching the membrane primarily induced extracellular Ca2+ entry through SA channels followed by Ca2+ releases from intracellular Ca2+ stores.

MECHANICS OF PATCH CLAMPED AND INTACT CELL-MEMBRANES IN RELATION TO SA CHANNEL ACTIVATION 査読

M SOKABE, K NUNOGAKI, K NARUSE, H SOGA

JAPANESE JOURNAL OF PHYSIOLOGY 43 ( Suppl 1 ) S197 - S204 1993年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：CENTER ACADEMIC PUBL JAPAN

Stretch activated (SA) channels are believed to be activated by tension in the membrane generated by membrane stretch. However, very few studies have been made on the quantitative estimation of the tension during membrane stretch. Here we present a method to evaluate the tension both in patch clamped and intact cell-membranes. The tension in patch clamped membranes was calculated from Laplace's law by knowing transmembrane pressure and the radius of patch-curvature. We also provide a simpler version for calculating the tension from the pressure and pipette radius. The tension in intact cell membranes was calculated from Hook's law based on the measurement of changes in cell surface area. The estimated tension required for activating SA channels in both types of membranes was found to be comparable suggesting that,the SA channel acts as a physiological mechanotransducer in intact cells.

DIFFERENTIAL RESPONSES OF CA-ACTIVATED K-CHANNELS TO BRADYKININ IN SENSORY NEURONS AND F-11 CELLS 査読

K NARUSE, DS MCGEHEE, GS OXFORD

AMERICAN JOURNAL OF PHYSIOLOGY 262 ( 2 ) C453 - C460 1992年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER PHYSIOLOGICAL SOC

The nonapeptide bradykinin (BK) excites a subset of dorsal root ganglion (DRG) neurons with putative nociceptive functions by stimulating an inward cation current. In addition, BK stimulates various intracellular signaling pathways including an elevation of intra-cellular Ca2+. In a DRG neuron x neuroblastoma hybrid cell (F-11), BK stimulates similar increases in intracellular [Ca2+] and inward current but also elicits a large transient outward current through Ca2+-activated K channels. We have investigated the mechanisms underlying differential expression of outward current responses in the two cell types at the single channel level. Although K(Ca) channel activity appears in inside-out patches from both cells exposed to Ca2+, BK applied to the extrapatch membrane of cell-attached patches activates K(Ca) channels in F-11 but not DRG neurons. Whereas single K(Ca) channels are quantitatively similar in terms of conductance, voltage-dependence, and sensitivity to tetraethylammonium, they differ in sensitivity to intracellular Ca2+. Channel activation in both cells requires at least four Ca2+ ions, but half-maximal activation occurs at slightly higher [Ca2+] for DRG neurons. The shift in the Ca2+ dose-response curve combined with the steep [Ca2+] dependence of channel open probability makes it less likely that a BK-induced rise in internal [Ca2+] induced will trigger a transient outward current and resultant hyperpolarization in a DRG neuron.

ELECTROPHYSIOLOGICAL ANALYSIS OF STRUCTURAL ASPECTS OF VOLTAGE-DEPENDENT SR K+ CHANNEL 査読

M SOKABE, M KASAI, K NOMURA, K NARUSE

COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-PHARMACOLOGY TOXICOLOGY & ENDOCRINOLOGY 98 ( 1 ) 23 - 30 1991年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

This article presents a brief review on the electrophysiological analysis of the structural aspects of the voltage-dependent SR (sarcoplasmic reticulum) K+ channel. In the first half, early attempts to determine the physical dimensions of the ion conducting mechanism such as the mouth, narrow tunnel, or ion selective filter of the channel, are reviewed. The depicted cartoon of the SR K+ channel, as an extremely short, busy district with a big mouth on each side, is quite similar to the recently-obtained reconstructed structural image of the acetylcholine receptor channel. In the latter half, we introduce our recent attempts to draw a physical image of the gating mechanism of the SR K+ channel. We examined, for example, the location of the gate and the voltage sensor, and the relationship between them. It is suggested that the gate and the sensor are connected tightly and that the sensor would be exposed to the surface of the lumen side of SR when the gate opens. Finally, the issue of substates in SR K+ channel is discussed. It is implied that the substate-conductances reflect a partial occlusion of the pore by an intermediate-open gate.

CLASSIFICATION OF THE INTRAFUSAL MUSCLE-FIBERS IN THE FROG-MUSCLE SPINDLE - HISTOCHEMICAL AND IMMUNOFLUORESCENT STUDIES 査読

A YOSHIMURA, N FUJITSUKA, M SOKABE, K NARUSE, K NOMURA, FH DIWAN, F ITO

JOURNAL OF ANATOMY 172 89 - 101 1990年10月

AMINOGLYCOSIDE BLOCKADE OF CA2+-ACTIVATED K+ CHANNEL FROM RAT-BRAIN SYNAPTOSOMAL MEMBRANES INCORPORATED INTO PLANAR BILAYERS 査読

K NOMURA, K NARUSE, K WATANABE, M SOKABE

JOURNAL OF MEMBRANE BIOLOGY 115 ( 3 ) 241 - 251 1990年5月

Effects of ions and drugs on the responses of sensory axon terminals of decapsulated frog muscle spindles 査読

Fumio Ito, Masahiro Sokabe, Kazushi Nomura, Keiji Naruse, Noriaki Fujitsuka, Atsushi Yoshimura

Neuroscience Research Supplements 12 ( C ) S15 - S26 1990年

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