Updated on 2026/09/03

写真a

 
KAIHARA KEIKO
 
Organization
Department of Comprehensive Technical Solutions Technical Expert staff
Position
Technical Expert staff
External link

Research Interests

  • 生理学

  • 生体医工学

Research Areas

  • Life Science / Physiology

 

Papers

  • Role of purinergic activation and TRPC3 channels in the Frank-Starling mechanism. International journal

    Yumiko Chiba, Keiko Kaihara, Gentaro Iribe

    The journal of physiological sciences : JPS   76 ( 1 )   100052 - 100052   2025.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    TRPC3 channels are involved in the physiological and pathological myocardial responses to mechanical loads. However, the involvement of TRPC3 in the response to acute stretch, that is, the Frank-Starling mechanism, has not been comprehensively elucidated. To elucidate this, we analyzed the response to stretch in isolated mouse ventricular cardiomyocytes. Our analysis revealed that TRPC3-deficient cells exhibited significantly lower cellular end-systolic elastance, an index of contractility, than wild-type cells owing to the absence of acute stretch-induced reactive oxygen species (ROS) production. Subsequently, we demonstrated that ATP released from pannexin-1 during stretch activates the TRPC3-NOX2 complex via P2Y signaling, thereby increasing ROS production. The results of this study show that TRPC3 plays a role in the Frank-Starling mechanism by mediating the mechanotransduction pathway of stretch-induced ROS production, which is a novel physiological role for TRPC3 in the heart.

    DOI： 10.1016/j.jphyss.2025.100052

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  • Direct Binding of Synaptopodin 2-Like Protein to Alpha-Actinin Contributes to Actin Bundle Formation in Cardiomyocytes Reviewed International journal

    Hiroshi Yamada, Hirona Osaka, Nanami Tatsumi, Miu Araki, Tadashi Abe, Keiko Kaihara, Ken Takahashi, Eizo Takashima, Takayuki Uchihashi, Keiji Naruse, Kohji Takei

    Cells   13 ( 16 )   1373 - 1373   2024.8

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：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

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  • Stretch‐induced reactive oxygen species contribute to the Frank–Starling mechanism Reviewed International journal

    Keiko Kaihara, Hiroaki Kai, Yumiko Chiba, Keiji Naruse, Gentaro Iribe

    The Journal of Physiology   602 ( 18 )   4347 - 4362   2023.4

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    Myocardial stretch physiologically activates NADPH oxidase 2 (NOX2) to increase reactive oxygen species (ROS) production. Although physiological low-level ROS are known to be important as signalling molecules, the role of stretch-induced ROS in the intact myocardium remains unclear. To address this, we investigated the effects of stretch-induced ROS on myocardial cellular contractility and calcium transients in C57BL/6J and NOX2-/- mice. Axial stretch was applied to the isolated cardiomyocytes using a pair of carbon fibres attached to both cell ends to evaluate stretch-induced modulation in the time course of the contraction curve and calcium transient, as well as to evaluate maximum cellular elastance, an index of cellular contractility, which is obtained from the end-systolic force-length relationship. In NOX2-/- mice, the peak calcium transient was not altered by stretch, as that in wild-type mice, but the lack of stretch-induced ROS delayed the rise of calcium transients and reduced contractility. Our mathematical modelling studies suggest that the augmented activation of ryanodine receptors by stretch-induced ROS causes a rapid and large increase in the calcium release flux, resulting in a faster rise in the calcium transient. The slight increase in the magnitude of calcium transients is offset by a decrease in sarcoplasmic reticulum calcium content as a result of ROS-induced calcium leakage, but the faster rise in calcium transients still maintains higher contractility. In conclusion, a physiological role of stretch-induced ROS is to increase contractility to counteract a given preload, that is, it contributes to the Frank-Starling law of the heart. KEY POINTS: Myocardial stretch increases the production of reactive oxygen species by NADPH oxidase 2. We used NADPH oxidase 2 knockout mice to elucidate the physiological role of stretch-induced reactive oxygen species in the heart. We showed that stretch-induced reactive oxygen species modulate the rising phase of calcium transients and increase myocardial contractility. A mathematical model simulation study demonstrated that rapid activation of ryanodine receptors by reactive oxygen species is important for increased contractility. This response is advantageous for the myocardium, which must contract against a given preload.

    DOI： 10.1113/jp284283

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  • High hydrostatic pressure induces slow contraction in mouse cardiomyocytes Reviewed International journal

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

    Biophysical Journal   122 ( 1 )   267 - 267   2023.1

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.bpj.2022.11.2940

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  • High hydrostatic pressure induces slow contraction in mouse cardiomyocytes. International journal

    Yohei Yamaguchi, Masayoshi Nishiyama, Hiroaki Kai, Toshiyuki Kaneko, Keiko Kaihara, Gentaro Iribe, Akira Takai, Keiji Naruse, Masatoshi Morimatsu

    Biophysical journal   62 ( Supplement 1-2 )   3286 - 3294   2022.7

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    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

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  • Ischemia Enhances the Acute Stretch-Induced Increase in Calcium Spark Rate in Ventricular Myocytes International journal

    Breanne A. Cameron, Hiroaki Kai, Keiko Kaihara, Gentaro Iribe, T. Alexander Quinn

    Frontiers in Physiology   11   289 - 289   2020.4

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media S.A.  

    DOI： 10.3389/fphys.2020.00289

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  • L-type calcium channel modulates mechanosensitivity of the cardiomyocyte cell line H9c2. Reviewed International journal

    Ken Takahashi, Shogo Hayashi, Mari Miyajima, Marei Omori, Jing Wang, Keiko Kaihara, Masatoshi Morimatsu, Chen Wang, Jian Chen, Gentaro Iribe, Keiji Naruse, Masahiro Sokabe

    Cell calcium   79   68 - 74   2019.5

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    The application of mechanical stimuli to cells often induce increases in intracellular calcium, affecting the regulation of a variety of cell functions. Although the mechanism of mechanotransduction-induced calcium increases has not been fully resolved, the involvement of mechanosensitive ion channels in the plasma membrane and the endoplasmic reticulum has been reported. Here, we demonstrate that voltage-gated L-type calcium channels play a critical role in the mechanosensitive calcium response in H9c2 rat cardiomyocytes. The intracellular calcium level in H9c2 cells increased in a reproducible dose-dependent manner in response to uniaxial stretching. The stretch-activated calcium response (SICR) completely disappeared in calcium-free medium, whereas thapsigargin and cyclopiazonic acid, inhibitors of sarcoendoplasmic reticulum calcium ATPase, partially reduced the SICR. These findings suggest that both calcium influx across the cell membrane and calcium release from the sarcoendoplasmic reticulum are involved in the SICR. Nifedipine, diltiazem, and verapamil, inhibitors of L-type calcium channels, reduced the SICR in a dose-dependent manner. Furthermore, small interfering RNA against the L-type calcium channel α1c subunit diminished the SICR dramatically. Nifedipine also diminished the mechanosensitivity of Langendorff-perfused rat heart. These results suggest that the SICR in H9c2 cardiomyocytes involves the activation of L-type calcium channels and subsequent calcium release from the sarcoendoplasmic reticulum.

    DOI： 10.1016/j.ceca.2019.02.008

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  • Mechano-sensitivity of mitochondrial function in mouse cardiac myocytes Reviewed International journal

    Gentaro Iribe, Keiko Kaihara, Yohei Yamaguchi, Michio Nakaya, Ryuji Inoue, Keiji Naruse

    Progress in Biophysics and Molecular Biology   130 ( Pt B )   315 - 322   2017.11

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ltd  

    DOI： 10.1016/j.pbiomolbio.2017.05.015

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

    Gentaro Iribe, Keiko Kaihara, Keiji Naruse

    Transactions of Japanese Society for Medical and Biological Engineering   52   44   2014.8

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    Language：English   Publisher：Japan Soc. of Med. Electronics and Biol. Engineering  

    DOI： 10.11239/jsmbe.52.SY-44

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  • Effect of azelnidipine and amlodipine on single cell mechanics in mouse cardiomyocytes Reviewed International journal

    Gentaro Iribe, Keiko Kaihara, Hiroshi Ito, Keiji Naruse

    EUROPEAN JOURNAL OF PHARMACOLOGY   715 ( 1-3 )   142 - 146   2013.9

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.ejphar.2013.05.030

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  • Improvement in Carbon Fiber Technique for Cardiomyocyte Mechanics and Mechano-Electric Coupling Study

    Iribe Gentaro, Kaneko Toshiyuki, Yamaguchi Yohei, Kaihara Keiko, Naruse Keiji

    BME   51   M - 32-M-32   2013

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    Language：English   Publisher：Japanese Society for Medical and Biological Engineering  

    DOI： 10.11239/jsmbe.51.M-32

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  • The mechanical stimulation of cells in 3D culture within a self-assembling peptide hydrogel Reviewed International journal

    Yusuke Nagai, Hidenori Yokoi, Keiko Kaihara, Keiji Naruse

    BIOMATERIALS   33 ( 4 )   1044 - 1051   2012.2

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    DOI： 10.1016/j.biomaterials.2011.10.049

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  • Effects of axial stretch on sarcolemmal BKCa channels in post-hatch chick ventricular myocytes Reviewed International journal

    Gentaro Iribe, Honghua Jin, Keiko Kaihara, Keiji Naruse

    EXPERIMENTAL PHYSIOLOGY   95 ( 6 )   699 - 711   2010.6

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    DOI： 10.1113/expphysiol.2009.051896

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  • Antigenic structures recognized by anti-beta 2-glycoprotein I auto-antibodies Reviewed International journal

    H Kasahara, E Matsuura, K Kaihara, D Yamamoto, K Kobayashi, J Inagaki, K Ichikawa, A Tsutsumi, S Yasuda, T Atsumi, T Yasuda, T Koike

    INTERNATIONAL IMMUNOLOGY   17 ( 12 )   1533 - 1542   2005.12

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    DOI： 10.1093/intimm/dxh330

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  • Significance of valine/leucine(247) polymorphism of beta(2)-glycoprotein I in antiphospholipid syndrome - Increased reactivity of anti-beta(2)-glycoprotein I autoantibodies to the valine(247) gamma(2)-glycoprotein I variant Reviewed International journal

    S Yasuda, T Atsumi, E Matsuura, K Kaihara, D Yamamoto, K Ichikawa, T Koike

    ARTHRITIS AND RHEUMATISM   52 ( 1 )   212 - 218   2005.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1002/art.20741

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  • An association of IgG anti-laminin-1 autoantibodies with endometriosis in infertile patients Reviewed International journal

    J Inagaki, M Sugiura-Ogasawara, M Nomizu, M Nakatsuka, K Ikuta, N Suzuki, K Kaihara, K Kobayashi, T Yasuda, Y Shoenfeld, K Aoki, E Matsuura

    HUMAN REPRODUCTION   18 ( 3 )   544 - 549   2003.3

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    DOI： 10.1093/humrep/deg148

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  • IgG anti-laminin-1 autoantibody and recurrent miscarriages. Reviewed

    Inagaki J, Matsuura E, Nomizu M, Sugiura-Ogasawara M, Katano K, Kaihara K, Kobayashi K, Yasuda T, Aoki K

    American journal of reproductive immunology (New York, N.Y. : 1989)   45   232 - 238   2001.4

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  • Proteolytic cleavage of beta 2-glycoprotein I: reduction of antigenicity and the structural relationship Reviewed

    E Matsuura, J Inagaki, H Kasahara, D Yamamoto, T Atsumi, K Kobayashi, K Kaihara, DD Zhao, K Ichikawa, A Tsutsumi, T Yasuda, DA Triplett, T Koike

    INTERNATIONAL IMMUNOLOGY   12 ( 8 )   1183 - 1192   2000.8

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    DOI： 10.1093/intimm/12.8.1183

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  • 抗リン脂質抗体と動脈硬化 Invited

    松浦栄次, 小林和子, 笠原順子, 貝原恵子, 小池隆夫

    リウマチ科   24 ( 4 )   378 - 384   2000

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MISC

  • メカニカル刺激と精子の運動特性

    川合智子, 森松賢順, 貝原恵子, 松浦宏治, 成瀬恵治

    日本生体医工学会大会プログラム・抄録集(Web)   64th   2025

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  • 開発蛍光遠心顕微鏡を用いた過重力下のマウス心筋細胞におけるカルシウム動態変化

    貝原恵子, 松浦宏治, 成瀬恵治

    日本生体医工学会大会プログラム・抄録集(Web)   64th   2025

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  • 心筋の伸展刺激誘発性ROS産生のメカノトランスダクション

    千葉弓子, 貝原恵子, 入部玄太郎

    日本生体医工学会大会プログラム・抄録集(Web)   63rd   2024

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  • 蛍光遠心顕微鏡を用いた過重力下のオルガネラ挙動およびカルシウム動態

    貝原恵子, 松浦宏冶, 成瀬恵治

    日本生体医工学会大会プログラム・抄録集(Web)   63rd   2024

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  • シナプトポディン2様タンパク質とアルファーアクチニンとの直接結合は心筋細胞のアクチン線維束形成に寄与する

    山田浩司, 大坂紘奈, 辰巳七海, 荒木美羽, 阿部匡史, 貝原恵子, 高橋賢, 高島英造, 内橋貴之, 成瀬恵治, 竹居孝二

    日本生化学会大会(Web)   97th   2024

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  • Single cell mechanics of human cardiomyocytes assessed by cellular force-length relationships(タイトル和訳中)

    Komatsu Hiroaki, Kotani Yasuhiro, Kaihara Keiko, Naruse Keiji, Kasahara Shingo, Iribe Gentaro

    The Journal of Physiological Sciences   73 ( Suppl.1 )   108 - 108   2023.5

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  • 新たな蛍光顕微鏡を用いた過重力下のオルガネラ挙動の解明

    貝原恵子, 松浦宏治, 成瀬恵治

    日本生体医工学会大会プログラム・抄録集(Web)   62nd   2023

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  • マウス心室心筋細胞におけるNOX4-TRPV1相互作用の単一細胞力学に対する役割(Role of NOX4-TRPV1 interaction on single cell mechanics in mouse ventricular cardiomyocytes)

    Kaihara Keiko, Naruse Keiji, Iribe Gentaro

    The Journal of Physiological Sciences   72 ( Suppl.1 )   117 - 117   2022.12

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  • マウス心筋細胞で認める高静水圧誘発性緩徐収縮(High hydrostatic pressure induces slow contraction in mouse cardiomyocytes)

    Yamaguchi Yohei, Nishiyama Masayoshi, Kai Hiroaki, Kaneko Toshiyuki, Kaihara Keiko, Iribe Gentaro, Takai Akira, Naruse Keiji, Morimatsu Masatoshi

    生物物理   62 ( Suppl.1-2 )   S458 - S458   2022.8

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  • 過重力下における細胞内小器官観測可能な新たな蛍光遠心顕微鏡の開発

    貝原恵子, 成瀬恵治

    日本生体医工学会大会プログラム・抄録集(Web)   61st   2022

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  • NOX4由来のROSが心筋細胞メカニクスに及ぼす影響(Effects of NOX4-induced ROS on single cell mechanics in mouse ventricular cardiomyocytes)

    Kaihara Keiko, Naruse Kenji, Iribe Gentaro

    The Journal of Physiological Sciences   71 ( Suppl.1 )   163 - 163   2021.8

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  • マウスにおいてNADPHオキシダーゼ4が心筋細胞メカニクスに及ぼす影響(Effects of NADPH oxidase (NOX) 4 on single cell mechanics in mouse ventricular cardiomyocytes)

    Kaihara Keiko, Naruse Keiji, Iribe Gentaro

    The Journal of Physiological Sciences   70 ( Suppl.1 )   S119 - S119   2020.3

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  • Involvement of myocardial acute stretch-induced ROS production in development of heart failure

    KAIHARA Keiko, NARUSE Keiji, IRIBE Gentaro

    日本生体医工学会大会プログラム・抄録集(Web)   59th   2020

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  • 心筋細胞におけるストレッチ誘発性ミトコンドリア過分極に関するパネキシンヘミチャネルの役割(Role of pannexin hemichannel on stretch-induced mitochondrial hyperpolarization in cardiomyocytes)

    Katsura Daisuke, Iribe Gentaro, Kaihara Keiko, Naruse Keiji

    The Journal of Physiological Sciences   69 ( Suppl.1 )   S202 - S202   2019.6

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  • 心筋細胞メカニクスにNADPHオキシダーゼ4が及ぼす影響(Single cell mechanics effects of NADPH oxidase(NOX) 4 in mouse ventricular cardiomyocytes)

    Kaihara Keiko, Iribe Gentaro, Kai Hiroaki, Naruse Keiji

    生物物理   58 ( Suppl.1-2 )   S431 - S431   2018.8

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  • 伸展刺激誘発性の活性酸素がマウス心筋calciumハンドリングに及ぼす影響(Effects of stretch-induced reactive oxygen species on calcium handling in mouse ventricular cardiomyocytes)

    Kai Hiroaki, Iribe Gentaro, Kaihara Keiko, Yamaguchi Yohei, Naruse Keiji

    The Journal of Physiological Sciences   68 ( Suppl.1 )   S142 - S142   2018.3

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  • 伸展刺激誘発性活性酸素がマウス心室心筋細胞の単細胞機構に及ぼす影響(Effects of stretch-induced reactive oxygen species on single cell mechanics in mouse ventricular cardiomyocytes)

    Kaihara Keiko, Iribe Gentaro, Hayama Yohei, Kai Hiroaki, Naruse Keiji

    The Journal of Physiological Sciences   68 ( Suppl.1 )   S118 - S118   2018.3

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  • Single cell mechanics effects of NADPH oxidase (NOX) 4 in mouse ventricular cardiomyocytes

    KAIHARA Keiko, IRIBE Gentaro, KAI Hiroaki, NARUSE Keiji

    生物物理(Web)   58 ( Supplement 1-2 )   2018

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  • 拡張型心筋症における心筋細胞活性酸素産生の伸展感受性(Stretch-induced increase in reactive oxygen species production in dilated cardiomyopathy)

    Kaihara Keiko, Naruse Keiji, Iribe Gentarou

    The Journal of Physiological Sciences   67 ( Suppl.1 )   S120 - S120   2017.3

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  • 伸展刺激誘発性ROS産生におけるミトコンドリアの役割

    貝原 恵子, 成瀬 恵治, 入部 玄太郎

    日本生理学雑誌   79 ( 1 )   42 - 43   2017.2

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  • 伸展刺激誘発性ROS産生におけるミトコンドリアの役割

    貝原恵子, 成瀬恵治, 入部玄太郎

    日本生理学雑誌(Web)   79 ( 1 )   2017

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  • 心筋の伸展刺激誘発性の活性酸素産生増加における呼吸鎖複合体の役割(Role of respiratory chain complexes in myocardial stretch-induced increase in reactive oxygen species)

    Kaihara Keiko, Naruse Keiji, Iribe Gentaro

    The Journal of Physiological Sciences   66 ( Suppl.1 )   S97 - S97   2016.3

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  • 心筋細胞におけるTRPC3を介した伸展刺激感知機構(TRPC3 contributes to a slow force response to stretch on mice cardiomyocytes)

    Yamaguchi Yohei, Iribe Gentaro, Kaihara Keiko, Naruse Keiji

    The Journal of Physiological Sciences   66 ( Suppl.1 )   S76 - S76   2016.3

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  • 自己集合性ペプチドハイドロゲル内で三次元培養された細胞への機械刺激

    永井 祐介, 横井 秀典, 貝原 恵子, 成瀬 恵治

    岡山医学会雑誌   126 ( 1 )   7 - 10   2014.4

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  • 伸展刺激によるカルシウムスパーク増加におけるミトコンドリアの役割(Role of mitochondria on stretch-induced increase in calcium spark rate)

    Kaihara Keiko, Naruse Keiji, Iribe Gentaro

    The Journal of Physiological Sciences   64 ( Suppl.1 )   S129 - S129   2014.3

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

    IRIBE Gentaro, KAIHARA Keiko, NARUSE Keiji

    日本生体医工学会大会プログラム・論文集(CD-ROM)   53rd   2014

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  • 伸展刺激誘発性カルシウムスパーク増加におけるミトコンドリアの役割

    貝原恵子, 成瀬恵治, 入部玄太郎

    日本生理学雑誌   76 ( 4 (Web) )   2014

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  • 自己集合性ペプチドハイドロゲル内で三次元培養された細胞への機械刺激

    永井祐介, 永井祐介, 横井秀典, 貝原恵子, 成瀬恵治

    岡山医学会雑誌   126 ( 1 )   2014

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  • 自己集合性ペプチドゲルを用いた3次元培養ストレッチシステムの開発

    永井祐介, 永井祐介, 徳山英二郎, 横井秀典, 貝原恵子, 高橋賢, 成瀬恵治

    再生医療   12   2013

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  • 単離心筋細胞への高伸展刺激負荷のための新たな細胞保持系の確立

    金子 智之, 入部 玄太郎, 貝原 恵子, 成瀬 恵治

    生体医工学   50 ( 4 )   398 - 398   2012.8

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  • 単離心筋細胞への高伸展刺激負荷のための新たな細胞保持系の確立

    金子智之, 入部玄太郎, 貝原恵子, 成瀬恵治

    生体医工学   50 ( 4 )   2012

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  • Effects of azelnidipine on single cardiomyocyte mechanics

    G. Iribe, K. Kaihara, H. Ito, K. Naruse

    EUROPEAN HEART JOURNAL   32   887 - 887   2011.8

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  • 心室筋細胞の収縮性に対するアゼルニジピンの影響

    貝原恵子, 入部玄太郎, 成瀬恵治

    日本生理学雑誌   73 ( 2 )   2011

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  • 0235 Development of new peptide scaffold for 3-D cell culturing under mechanical stimulation

    NAGAI Yusuke, KAIHARA Keiko, YOKOI Hidenori, UESUGI Koji, NARUSE Keiji

    2009 ( 22 )   219 - 219   2010.1

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  • 機械刺激下での3次元培養を目的としたペプチドスキャフォールドの開発

    永井祐介, 永井祐介, 貝原恵子, 横井秀典, 上杉晃司, 成瀬恵治

    バイオエンジニアリング講演会講演論文集   22nd   2010

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  • 機械的刺激下での三次元細胞培養のための自己集合性ペプチドナノ繊維足場(Self-assembling peptide nanofiber scaffold for 3-D cell culturing under mechanical stimulation)

    Nagai Yusuke, Kaihara Keiko, Yokoi Hidenori, Uesugi Koji, Naruse Keiji

    Organ Biology   16 ( 1 )   149 - 149   2009.4

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  • 孵化後のトリ心筋SAKCAチャネルの伸展感受性

    入部玄太郎, JIN Honghua, 永井祐介, 貝原恵子, 成瀬恵治

    日本生体医工学会大会プログラム・論文集(CD-ROM)   48th   2009

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  • 志賀毒素誘導の腎上皮様Vero細胞のアポトーシスにおけるAktの関与(Involvement of Akt in Shiga toxin-induced apoptosis of renal epithelial cells)

    Kobuchi Hirotsugu, Kaihara Keiko, Utsumi Kozo, Yasuda Tatsuji

    生化学   76 ( 8 )   1089 - 1089   2004.8

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  • 志賀毒素はJNK依存的Bcl-2リン酸化を介してアポトーシスを誘導する

    小淵浩嗣, 貝原恵子, 保田立二

    日本細菌学雑誌   59 ( 1 )   2004

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  • 志賀毒素誘導アポトーシスにおけるJNK活性化の意義

    小淵浩嗣, 貝原恵子, 内海耕ぞう, 保田立二

    生化学   76 ( 3 )   2004

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  • 志賀毒素のアポトーシス誘導機構におけるJNKの関与

    小淵浩嗣, 貝原恵子, 保田立二

    日本細菌学雑誌   58 ( 1 )   2003

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  • 志賀毒素によるJNKを介したアポトーシス誘導

    小淵浩嗣, 貝原恵子, 内海耕ぞう, 保田立二

    生化学   74 ( 8 )   2002

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  • IgG抗ラミニン-1自己抗体 反復流産及び子宮内膜症の危険因子

    稲垣 純子, 松浦 栄次, 小笠原 真弓, 野水 基義, 片野 衣江, 貝原 恵子, 小林 和子, 保田 立二, 青木 耕治

    日本免疫学会総会・学術集会記録   31   76 - 76   2001.12

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  • β2-グリコプロテインIに特異的な酸化脂質リガンドと自己抗体の動脈硬化進展への関与

    劉 慶平, 松浦 栄次, 小林 和子, 稲垣 純子, 貝原 恵子, 笠原 順子, 保田 立二, 小池 隆夫

    日本免疫学会総会・学術集会記録   31   76 - 76   2001.12

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  • A specific ligand for β<inf>2</inf>-glycoprotein I mediates autoantibody-dependent uptake of oxidized low density lipoprotein by macrophages

    Kazuko Kobayashi, Eiji Matsuura, Qingping Liu, Jun Ichi Furukawa, Keiko Kaihara, Junko Inagaki, Tatsuya Atsumi, Nobuo Sakairi, Tatsuji Yasuda, Dennis R. Voelker, Takao Koike

    Journal of Lipid Research   42   697 - 709   2001.6

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  • 抗リン脂質抗体症候群患者血清中に抗スルファチド抗体の特異性

    貝原 恵子, 松浦 栄次, 小林 和子, 稲垣 純子, 劉 慶平, 保田 立二, 宮脇 昌二, 小池 隆夫

    リウマチ   41 ( 2 )   392 - 392   2001.4

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  • 抗リン脂質抗体症候群における動脈硬化発症への酸化コレステロールエステルの関与

    小林 和子, 松浦 栄次, 劉 慶平, 貝原 恵子, 稲垣 純子, 保田 立二, 小池 隆夫

    リウマチ   41 ( 2 )   391 - 391   2001.4

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  • IgG anti-laminin-1 autoantibody and recurrent miscarriages

    Junko Inagaki, Eiji Matsuura, Eiji Matsuura, Motoyoshi Nomizu, Mayumi Sugiura-Ogasawara, Kinue Katano, Keiko Kaihara, Kazuko Kobayashi, Tatsuji Yasuda, Koji Aoki

    American Journal of Reproductive Immunology   45   232 - 238   2001.1

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  • IgG抗ラミニン-1自己抗体 反復流産および子宮内膜症の危険因子

    稲垣純子, 松浦栄次, 小笠原真弓, 野水基義, 片野衣江, 貝原恵子, 小林和子, 保田立二, 青木耕治

    日本免疫学会総会・学術集会記録   31   2001

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  • 抗リン脂質抗体症候群患者血清中に抗スルファチド抗体の特異性

    貝原恵子, 松浦栄次, 小林和子, 稲垣純子, 劉慶平, 保田立二, 宮脇昌二, 小池隆夫

    リウマチ   41 ( 2 )   2001

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  • 抗リン脂質抗体症候群における動脈硬化発症への酸化コレステロールエステルの関与

    小林和子, 松浦栄次, 劉慶平, 貝原恵子, 稲垣純子, 保田立二, 小池隆夫

    リウマチ   41 ( 2 )   2001

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  • β2-グリコプロテインIに特異的な酸化脂質リガンドと自己抗体の動脈硬化進展への関与

    劉慶平, 松浦栄次, 小林和子, 稲垣純子, 貝原恵子, 笠原順子, 保田立二, 小池隆夫

    日本免疫学会総会・学術集会記録   31   2001

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  • 抗リン脂質抗体症候群における血中酸化LDLの臨床的意義

    笠原 順子, 松浦 栄次, 趙 丹丹, 小林 和子, 劉 慶平, 貝原 恵子, 稲垣 純子, 保田 立二, 槇野 博史

    日本免疫学会総会・学術集会記録   30   108 - 108   2000.11

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  • β2グリコプロテインI valine/leucine247遺伝子多型が抗β2-glycoprotein I抗体の結合性に与える影響

    保田 晋助, 渥美 達也, 松浦 栄次, 貝原 恵子, 竹内 理恵, 堀田 哲也, 三好 義範, 小椋 庸隆, 天崎 吉晴, 市川 健司

    日本免疫学会総会・学術集会記録   30   104 - 104   2000.11

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  • 自己免疫疾患患者おける抗スルファチド抗体の出現 SLE及び抗リン脂質抗体症候群における解析

    貝原 恵子, 松浦 栄次, 小林 和子, 稲垣 純子, 劉 慶平, 保田 立二, 宮脇 昌二, 小池 隆夫

    日本免疫学会総会・学術集会記録   30   107 - 107   2000.11

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  • 抗リン脂質抗体症候群における動脈血栓への抗β2-グリコプロテインI自己抗体の関与

    小林 和子, 松浦 栄次, 劉 慶平, 貝原 恵子, 稲垣 純子, 保田 立二, 小池 隆夫

    日本免疫学会総会・学術集会記録   30   107 - 107   2000.11

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  • Valine/leucine(247) polymorphism of beta 2-glycoprotein 1 affects the reactivity of anti-beta 2-glycoprotein 1 antibodies.

    S Yasuda, T Atsumi, K Ichikawa, E Matsuura, K Kaihara, T Yasuda, Y Amasaki, T Koike

    ARTHRITIS AND RHEUMATISM   43 ( 9 )   S404 - S404   2000.9

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  • 抗β2-グリコプロテインI・酸化LDL抗体による動脈硬化の発症機序

    小林 和子, 松浦 栄次, 劉 慶平, 貝原 恵子, 稲垣 純子, 保田 立二, 小池 隆夫

    リウマチ   40 ( 2 )   385 - 385   2000.4

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  • 自己抗原の発現に関与するβ2-グリコプロテインIのドメインIV-V間の相互作用

    貝原 恵子, 松浦 栄次, 山本 大助, 小林 和子, 稲垣 純子, 劉 慶平, 保田 立二, 小池 隆夫

    リウマチ   40 ( 2 )   387 - 387   2000.4

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  • 自己免疫疾患患者おける抗スルファチド抗体の出現 SLEおよび抗リン脂質抗体症候群における解析

    貝原恵子, 松浦栄次, 小林和子, 稲垣純子, 劉慶平, 保田立二, 宮脇昌二, 小池隆夫

    日本免疫学会総会・学術集会記録   30   2000

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  • 抗リン脂質抗体症候群における血中酸化LDLの臨床的意義

    笠原順子, 松浦栄次, ちょう丹丹, 小林和子, 劉慶平, 貝原恵子, 稲垣純子, 保田立二, ほう野博史

    日本免疫学会総会・学術集会記録   30   2000

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  • β2グリコプロテインI valine/leucine247遺伝子多型が抗β2-glycoprotein I抗体の結合性に与える影響

    保田晋助, 渥美達也, 松浦栄次, 貝原恵子, 竹内理恵, 堀田哲也, 三好義範, 保田立二, 小池隆夫

    日本免疫学会総会・学術集会記録   30   2000

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  • 抗β2-グリコプロテインI・酸化LDL抗体による動脈硬化の発症機序

    小林和子, 松浦栄次, 劉慶平, 貝原恵子, 稲垣純子, 保田立二, 小池隆夫

    リウマチ   40 ( 2 )   2000

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  • 抗リン脂質抗体症候群における動脈血栓への抗β2-グリコプロテインI自己抗体の関与

    小林和子, 松浦栄次, 劉慶平, 貝原恵子, 稲垣純子, 保田立二, 小池隆夫

    日本免疫学会総会・学術集会記録   30   2000

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  • 自己抗原の発現に関与するβ2-グリコプロテインIのドメインIV-V間の相互作用

    貝原恵子, 松浦栄次, 山本大助, 小林和子, 稲垣純子, 劉慶平, 保田立二, 小池隆夫

    リウマチ   40 ( 2 )   2000

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  • 抗リン脂質抗体と動脈硬化

    松浦栄次, 小林和子, 笠原順子, 貝原恵子, 小池隆夫

    月刊リウマチ科   24 ( 4 )   2000

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  • 抗β2-グリコプロテインI抗体の動脈硬化への関与(II) マクロファージによる酸化LDLの取り込みの機序

    小林 和子, 松浦 栄次, 劉 慶平, 貝原 恵子, 稲垣 純子, 保田 立二, 小池 隆夫

    日本免疫学会総会・学術集会記録   29   35 - 35   1999.10

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  • cryptic epitopeの発現に関与するβ2-グリコプロテインIのドメインIV-V間の相互作用

    貝原 恵子, 松浦 栄次, 山本 大助, 小林 和子, 稲垣 純子, 劉 慶平, 保田 立二, 小池 隆夫

    日本免疫学会総会・学術集会記録   29   35 - 35   1999.10

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  • 抗β2-グリコプロテインI抗体の動脈硬化への関与I.酸化LDL由来のリガンドの精製と自己抗体の反応性

    松浦 栄次, 小林 和子, 劉 慶平, 貝原 恵子, 稲垣 純子, 保田 立二, 小池 隆夫

    日本免疫学会総会・学術集会記録   29   35 - 35   1999.10

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  • 抗リン脂質抗体の動脈硬化の進展への関与

    小林 和子, 松浦 栄次, 稲垣 純子, 貝原 恵子, 保田 立二, 小池 隆夫

    リウマチ   39 ( 2 )   322 - 322   1999.4

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  • plasminによる限定分解 自己抗原であるβ2-グリコプロテイン1の抗原性の消失

    松浦 栄次, 稲垣 純子, 小林 和子, 貝原 恵子, 保田 立二, 笠原 英樹, 市川 健司, 堤 明人, 小池 隆夫

    リウマチ   39 ( 2 )   323 - 323   1999.4

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  • 抗β2-グリコプロテインI抗体の動脈硬化への関与 I. 酸化LDL由来のリガンドの精製と自己抗体の反応性

    松浦栄次, 小林和子, 劉慶平, 貝原恵子, 稲垣純子, 保田立二, 小池隆夫

    日本免疫学会総会・学術集会記録   29   1999

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  • 抗β2-グリコプロテインI抗体の動脈硬化への関与 II. マクロファージによる酸化LDLの取り込みの機序

    小林和子, 松浦栄次, 劉慶平, 貝原恵子, 稲垣純子, 保田立二, 小池隆夫

    日本免疫学会総会・学術集会記録   29   1999

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  • cryptic epitopeの発現に関与するβ2-グリコプロテインIのドメインIV-V間の相互作用

    貝原恵子, 松浦栄次, 山本大助, 小林和子, 稲垣純子, 劉慶平, 保田立二, 小池隆夫

    日本免疫学会総会・学術集会記録   29   1999

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  • 抗β2-グリコプロテインI抗体の反応特異性の解析:酸性リン脂質由来の脂肪酸の関与

    小林 和子, 松浦 栄次, 稲垣 純子, 貝原 恵子, 保田 立二, 小池 隆夫

    日本臨床免疫学会会誌   ( 26回抄録集 )   242 - 242   1998.10

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  • 自己抗原であるβ2-グリコプロテインIの三次構造

    山本 大助, 松浦 栄次, 貝原 恵子, 稲垣 純子, 小林 和子, 保田 立二, 小池 隆夫

    日本臨床免疫学会会誌   ( 26回抄録集 )   239 - 239   1998.10

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  • 自己抗原であるβ2-グリコプロテインIの不活化:plasminによる酵素的開裂に伴う抗原性の消失

    松浦 栄次, 稲垣 純子, 小林 和子, 貝原 恵子, 保田 立二, 山本 大助, 笠原 英樹, 市川 健司, 堤 明人, 小池 隆夫

    日本臨床免疫学会会誌   ( 26回抄録集 )   242 - 242   1998.10

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  • 自己抗原であるβ2-グリコプロテインIの3次構造

    山本大助, 松浦栄次, 貝原恵子, 稲垣純子, 小林和子, 保田立二, 小池隆夫

    日本免疫学会総会・学術集会記録   28   1998

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  • 自己抗原であるβ2-グリコプロテインIの不活化 plasminによる酵素的開裂に伴う抗原性の消失

    松浦栄次, 稲垣純子, 小林和子, 貝原恵子, 保田立二, 山本大助, 笠原英樹, 市川健司, 小池隆夫

    日本免疫学会総会・学術集会記録   28   1998

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  • 抗β2-グリコプロテインI抗体の反応特異性の解析 酸性リン脂質由来の脂肪酸の関与

    小林和子, 松浦栄次, 稲垣純子, 貝原恵子, 保田立二, 小池隆夫

    日本免疫学会総会・学術集会記録   28   1998

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  • Treatment of experimental retrovirus infection by toxin gene binding electropositive electric charge liposome.

    李振泰, 塔郷, 渡来仁, 貝原(細谷)恵子, 小沼操, 柿谷均, 保田立二

    日本分子生物学会年会プログラム・講演要旨集   19th   1996

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Awards

  • コニカミノルタ科学技術振興財団 日本生体医工学会大会奨励賞

    2026.6   第65回日本生体医工学会大会   独自開発蛍光遠心顕微鏡を用いたマウス心筋細胞の過重力下におけるカルシウム動態変化

    貝原恵子, 松浦宏冶, 成瀬恵治

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  • コニカミノルタ科学技術振興財団・日本生体医工学会大会奨励賞

    2024.5   第63回日本生体医工学会大会   蛍光遠心顕微鏡を用いた過重力下のオルガネラ挙動およびカルシウム動態

    貝原恵子, 松浦宏冶, 成瀬恵治

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  • 最優秀若手講演奨励賞

    2022.10   第45回日本生体医工学会中国四国支部大会   ヒト単離心筋細胞における長さ張力関係を用いた力学機能評価

    小松弘明, 小谷恭弘, 貝原恵子, 成瀬恵治, 笠原真悟, 入部玄太郎

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  • 若手講演奨励賞

    2019.10   第42回日本生体医工学会中国四国支部大会   心筋バイオメカニクス制御におけるプリン作動性シグナリングの役割

    赤嶺透子, 入部玄太郎, 貝原恵子, 桂大輔, 成瀬恵治

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Research Projects

  • ミトコンドリアの伸展感受性による新しい心臓メカノエナジェティクス制御機構の解明

    Grant number：26K15617  2026.04 - 2029.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    入部 玄太郎, 貝原 恵子, 川合 智子, 千葉 弓子

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    Grant amount：\4550000 （ Direct expense: \3500000 、 Indirect expense：\1050000 ）

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  • Effects of gravity-mediated mechanotransduction on cardiomyocyte calcium handling

    Grant number：24K15698  2024.04 - 2027.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    貝原 恵子, 成瀬 恵治, 松浦 宏治

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    Grant amount：\4680000 （ Direct expense: \3600000 、 Indirect expense：\1080000 ）

    本研究では、重力変化が、心筋の収縮・拡張に伴う興奮収縮連関に関与する細胞内カルシウム濃度変化の制御（カルシウムハンドリング）に及ぼす影響についての詳細を明らかにするために、独自開発した蛍光遠心顕微鏡や、疑似微小重力装置搭載型蛍光顕微鏡を用いて測定を行った。細胞を播種した密閉チャンバーを用いて過・微重力負荷下でリアルタイム測定を行うため、接着培養可能でかつ拍動（カルシウムトランジェント：自発的な活動電位によって惹起される細胞質内のカルシウム濃度上昇）のあるマウス新生児由来心筋細胞を用いた。カルシウム指示薬Flou-4を用いて心拍に対応する細胞質内のカルシウム濃度変化測定により、リアルタイムにて過・微重力負荷瞬間のカルシウム動態をとらえることが可能となった。
    新たに開発した蛍光遠心顕微鏡を用いてリアルタイム測定を行ったところ、マウス新生児由来心筋細胞のカルシウムトランジェント振幅数について次に記載する応答が確認できた。①過重力（5G）負荷数秒後にはカルシウムトランジェント振幅数が負荷前と比較して3割ほど優位に上昇した。②細胞にて重力感知能力があるとの報告のある微小管を阻害してもカルシウムトランジェント振幅数に影響はなかった。③機械感受性チャネル阻害剤であるGsMTx-4を用いた際には、過重力負荷による優位なカルシウムトランジェント振幅数の上昇が消失した。
    つまり、単一の心筋細胞にて過重力を感知するシステム保有の可能性と、そのメカニズムに機械感受性チャネルの関与が示唆された。

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  • The Role of ROS Signaling in Regulating Myocardial Mechanosensitive Responses and Its Application to Heart Failure Therapy

    Grant number：21K12640  2021.04 - 2024.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Iribe Gentaro

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    Grant amount：\4290000 （ Direct expense: \3300000 、 Indirect expense：\990000 ）

    Myocardial stretch-induced ROS production is thought to be physiological ROS, but their role is not well understood. In this study, the signaling pathway from myocardial stretch to ROS production was clarified, and it was shown that stretch-induced ROS maintains myocardial contractility during stretch by promoting calcium release from reanodine receptors during myocardial stretch. Furthermore, our results suggest that the excessive ROS production (oxidative stress) associated with chronic pressure overload-induced heart failure may be initiated by an enhancement of physiological stretch-induced ROS production.

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  • Evaluation of isolated human cardiomyocyte function via the force&#8211;length relationship

    Grant number：21K08866  2021.04 - 2024.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Komatsu Hiroaki

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    Grant amount：\4160000 （ Direct expense: \3200000 、 Indirect expense：\960000 ）

    In this study, we successfully isolated cardiomyocytes from resected myocardial tissue of patients with congenital heart disease and, for the first time, demonstrated that these cells obey the Frank-Starling mechanism under electrical and mechanical stretch stimulation. Using Modified Del Nido cardioplegia and a BDM-containing buffer, we maintained the contractile responsiveness of pediatric cardiomyocytes. Immunostaining revealed immature microtubule networks, suggesting that physiological responses can occur even in structurally underdeveloped cells.

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  • Investigation of NOX4-mediated mechanotransduction in mechanically-induced cardiac failure

    Grant number：20K12598  2020.04 - 2023.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Kaihara Keiko

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    Grant amount：\4290000 （ Direct expense: \3300000 、 Indirect expense：\990000 ）

    ROS derived from NOX4 was produced by stretch stimulation, activated TRPV1, and affected calcium transient waveforms.This demonstrates that NOX4 and TRPV1 are involved in enhancing contractile force during stretching. Additionally, it was shown that NOX4 and TRPV1 localize to mitochondria and influence mitochondrial membrane potential. Thus, NOX4 and TRPV1 may be involved in the Frank-Starling law.Furthermore, in subacute load responses, the significant increase in contractile force observed in WT cells several minutes after stretching was absent in cardiomyocytes derived from NOX4KO and TRPV1KO mice. However, in the heart failure model of NOX4KO mice, the disease progressed.
    The role of NOX4 and TRPV1 in mechanotransduction and their association with disease pathophysiology remain topics for future research.

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  • Physiological and pathophysiological role of NOX4 in cardiac mechano-transduction

    Grant number：17K01359  2017.04 - 2020.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Kaihara Keiko

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    Grant amount：\4550000 （ Direct expense: \3500000 、 Indirect expense：\1050000 ）

    Reactive oxygen species (ROS) synthesized by NADPH oxidase (NOX) in vivo is a very important physiologically active substance. Although, myocardial stretch-induced ROS production via NOX2 modulates Ca2+ handling and cellular contractility, behavior of NOX4 is unknown. In the present study, we investigated the physiological and pathophysiological role of NOX4 in cardiac mechano-transduction.
    Ventricular cells isolated were subjected to 5-10% axial stretch with the cardiomyocyte stretch system, were measured ROS production, Ca2+ spark rate, mitochondrial membrane potential and cellular contractility. Cellular contractility and ROS production were significantly suppressed in NOX2 KO and NOX4 KO, but Ca2+ spark rate was suppressed only in NOX2 KO. The results suggest that role of NOX4 during stretch is different from that of NOX2. On the other hand, from the results of TAC model mice, there was an effect of NOX4 on overload, but details could not be clarified.

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  • Development of a three dimensional stretchcell culture system with a self-assembling peptide scaffold

    Grant number：23650264  2011 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    NARUSE Keiji, KAIHARA Keiko, NAGAI Yusuke

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    Grant amount：\3770000 （ Direct expense: \2900000 、 Indirect expense：\870000 ）

    For effective tissue regeneration, we have developed a three dimensional cell culture system capable of mechanical cell stimulation. The degree of ERK phosphorylation and the cell proliferation ratio of three dimensionally cultured mouse skeletal muscle cells were improved by stretch stimulations in a system composed of newly developed self-assembling peptide gel and stretch chamber. These results demonstrated that the three dimensional stretch cell culture system was able to transmit mechanical stimulation to the cell and control its behaviors such as cell proliferation.

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