研究者詳細 - 中山　真彰

論文 - 中山　真彰

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Construction and Characterization of the PGN_0296 Mutant of Porphyromonas gingivalis 査読

Abu Saleh Muhammad Shahriar, Shintaro Ono, Masaaki Nakayama, Naoko Ohara and Naoya Ohara

Journal of Oral Biosciences 2020年10月

The fungal metabolite (+)-terrein abrogates osteoclast differentiation via suppression of the RANKL signaling pathway through NFATc1. 査読

Saki Nakagawa, Kazuhiro Omori, Masaaki Nakayama, Hiroki Mandai, Satoshi Yamamoto, Hiroya Kobayashi, Hidefumi Sako, Kyosuke Sakaida, Hiroshi Yoshimura, Satoki Ishii, Soichiro Ibaragi, Kimito Hirai, Keisuke Yamashiro, Tadashi Yamamoto, Seiji Suga, Shogo Takashiba

Int Immunopharmacol. 83 2020年6月

The fungal metabolite (+)-terrein abrogates osteoclast differentiation via suppression of the RANKL signaling pathway through NFATc1. 国際誌

International immunopharmacology 83 106429 - 106429 2020年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Pathophysiological bone resorption is commonly associated with periodontal disease and involves the excessive resorption of bone matrix by activated osteoclasts. Receptor activator of nuclear factor (NF)-κB ligand (RANKL) signaling pathways have been proposed as targets for inhibiting osteoclast differentiation and bone resorption. The fungal secondary metabolite (+)-terrein is a natural compound derived from Aspergillus terreus that has previously shown anti-interleukin-6 properties related to inflammatory bone resorption. However, its effects and molecular mechanism of action on osteoclastogenesis and bone resorption remain unclear. In the present study, we showed that 10 µM synthetic (+)-terrein inhibited RANKL-induced osteoclast formation and bone resorption in a dose-dependent manner and without cytotoxicity. RANKL-induced messenger RNA expression of osteoclast-specific markers including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), the master regulator of osteoclastogenesis, cathepsin K, tartrate-resistant acid phosphatase (Trap) was completely inhibited by synthetic (+)-terrein treatment. Furthermore, synthetic (+)-terrein decreased RANKL-induced NFATc1 protein expression. This study revealed that synthetic (+)-terrein attenuated osteoclast formation and bone resorption by mediating RANKL signaling pathways, especially NFATc1, and indicated the potential effect of (+)-terrein on inflammatory bone resorption including periodontal disease.

DOI： 10.1016/j.intimp.2020.106429

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PCRをベースとしたLautropia mirabilisの簡便な検出法と分離法の検討

佐藤あやめ, 中山真彰, 中川美緒, 小崎弘貴, 室美里, 曽我賢彦, 大原直也

日本細菌学雑誌 75 ( 1 ) 66 - 66 2020年1月

Construction and characterization of a PGN_0297 mutant of Porphyromonas gingivalis: evidence for contribution of PGN_0297 to gingipain activity 査読

Shintaro Ono, Masaaki Nakayama, Masato Tachibana, Abu Saleh Muhammad Shahriar, Wang Heling, Shogo Takashiba, and Naoya Ohara

Acta Medica Okayama 2019年3月

Construction and characterization of a PGN_0297 mutant of Porphyromonas gingivalis: Evidence of the contribution of PGN_0297 to gingipain activity

Shintaro Ono, Masaaki Nakayama, Masato Tachibana, Abu Saleh Muhammad Shahriar, Wang Heling, Shogo Takashiba, Naoya Ohara

Acta Medica Okayama 73 ( 4 ) 315 - 323 2019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：Okayama University

The periodontal pathogen Porphyromonas gingivalis shows colonial pigmentation on blood agar and produces gingipains (Kgp, RgpA, and RgpB), cysteine proteases involved in an organism's virulence and pigmentation. We showed previously that deletion of the PGN_0300 gene abolished the pigmentation activity and reduced the proteolytic activity of gingipains. The role of the PGN_0297 gene, which consists of an operon with the PGN_0300 gene, is unclear. Herein we examined the effect of PGN_0297 gene deletion on the pigmentation and proteolytic activities and transcriptional levels of gingipains. A PGN_0297 gene deletion mutant (ΔPGN_0297) did not exhibit the pigmentation. The proteolytic activity of the gingipains was decreased in the culture supernatant and on the cell surface of ΔPGN_0297. The mutant ΔPGN_0297 failed to attenuate Akt phosphorylation at Thr308 and Ser473, but both phosphorylations were attenuated in the wild-type and its complementation strain. The deletion of PGN_0297 gene did not substantially affect the transcriptional levels of the gingipain genes kgp, rgpA, and rgpB. Taken together, these results indicate that PGN_0297 is closely involved in the secretion and maturation of gingipains.

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Fungal metabolite (+)-terrein suppresses IL-6/sIL-6R-induced CSF1 secretion by inhibiting JAK1 phosphorylation in human gingival fibroblasts. 査読国際誌

Satoshi Yamamoto, Kazuhiro Omori, Hiroki Mandai, Masaaki Nakayama, Saki Nakagawa, Hiroya Kobayashi, Tadashi Kunimine, Hiroshi Yoshimura, Kyosuke Sakaida, Hidefumi Sako, Soichiro Ibaragi, Tadashi Yamamoto, Hiroshi Maeda, Seiji Suga, and Shogo Takashiba

Heliyon 4 ( 11 ) e00979 2018年11月

Fungal metabolite (

HELIYON 4 ( 11 ) 2018年11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 SCI LTD

Control of bacterial infection-induced inflammatory responses is one of the effective therapeutic approaches of periodontal diseases. Natural products such as lipid mediators and metabolites from microorganisms have been used for decreasing inflammation. We previously reported that (+)-terrein inhibited activation of STAT3 and ERK1/2 in interleukin-6 (IL-6) signaling cascade, leading to prevent vascular endothelial growth factor (VEGF) secretion in human gingival fibroblasts (HGFs). However, little is still known about the role of (+)-terrein on inflammatory responses. In this study, we provided the possibility of novel action that (+)-terrein inhibits activation of Janus-activated kinase 1 (JAK1), which has a central function in IL-6 signaling cascade, and alters expression of mRNAs and proteins induced by IL-6/soluble IL-6 receptor (sIL6R) stimulation in HGFs. First, we performed PCR array to examine IL-6/sIL6R-induced mRNA expression, and then expression of mRNA and protein of colony stimulating factor-1 (CSF1) and VEGF were clearly determined by quantitative RT-PCR and ELISA, respectively. Treatment with (+)-terrein suppressed expression of mRNA and protein of CSF1 and VEGF by IL-6/sIL-6R stimulation. Next, to test the effect of (+)-terrein on IL-6/sIL-6R signaling cascade, we demonstrated whether (+)-terrein affects phosphorylation of JAK1 and its downstream proteins, Akt and SHP-2. Western blotting revealed that (+)-terrein inhibited IL-6/sIL-6R-induced phosphorylation of JAK1, Akt, and SHP-2. Therefore, (+)-terrein suppresses IL-6/sIL-6R-induced expression of CSF1 and VEGF via inhibition of JAK1, Akt, and SHP-2. Based on our results, we suggest that (+)-terrein is a candidate compound for anti-inflammatory effect associated with IL-6 signaling.

DOI： 10.1016/j.heliyon.2018.e00979

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Novel function of Porphyromonas gingivalis gingipains in the PI3K/Akt signaling pathway 招待査読

Nakayama Masaaki, Ohara Naoya

JOURNAL OF ORAL BIOSCIENCES 59 ( 3 ) 131 - 134 2017年8月

Involvement of an Skp-Like Protein, PGN_0300, in the Type IX Secretion System of Porphyromonas gingivalis 査読

Yuko Taguchi, Keiko Sato, Hideharu Yukitake, Tetsuyoshi Inoue, Masaaki Nakayama, Mariko Naito, Yoshio Kondo, Konami Kano, Tomonori Hoshino, Koji Nakayama, Shogo Takashiba, Naoya Ohara

INFECTION AND IMMUNITY 84 ( 1 ) 230 - 240 2016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：AMER SOC MICROBIOLOGY

The oral Gram-negative anaerobic bacterium Porphyromonas gingivalis is an important pathogen involved in chronic periodontitis. Among its virulence factors, the major extracellular proteinases, Arg-gingipain and Lys-gingipain, are of interest given their abilities to degrade host proteins and process other virulence factors. Gingipains possess C-terminal domains (CTDs) and are translocated to the cell surface or into the extracellular milieu by the type IX secretion system (T9SS). Gingipains contribute to the colonial pigmentation of the bacterium on blood agar. In this study, Omp17, the PGN_0300 gene product, was found in the outer membrane fraction. A mutant lacking Omp17 did not show pigmentation on blood agar and showed reduced proteolytic activity of the gingipains. CTD-containing proteins were released from bacterial cells without cleavage of the CTDs in the omp17 mutant. Although synthesis of the anionic polysaccharide (A-LPS) was not affected in the omp17 mutant, the processing of and A-LPS modification of CTD-containing proteins was defective. PorU, a C-terminal signal peptidase that cleaves the CTDs of other CTD-containing proteins, was not detected in any membrane fraction of the omp17 mutant, suggesting that the defective maturation of CTD-containing proteins by impairment of Omp17 is partly due to loss of function of PorU. In the mouse subcutaneous infection experiment, the omp17 mutant was less virulent than the wild type. These results suggested that Omp17 is involved in P. gingivalis virulence.

DOI： 10.1128/IAI.01308-15

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BCG thyX欠損株の作製とその性状解析

有村友紀, 中山真彰, 妹尾昌紀, 田川淳平, 中山浩次, 飯田征二, 大原直也

Journal of Oral Biosciences Supplement 2015 330 - 330 2015年9月

BCGにおけるcyclic-di-GMP菌体内合成の影響

妹尾昌紀, 中山真彰, 有村友紀, 飯田征二, 大原直也

Journal of Oral Biosciences Supplement 2015 331 - 331 2015年9月

Involvement of an Skp-like protein, PGN_0300, in the type IX secretion system of Porphyromonas gingivalis 査読

Yuko Taguchi , Keiko Sato , Hideharu Yukitake , Tetsuyoshi Inoue , Masaaki Nakayama , Mariko Naito , Yoshio Kondo , Konami Kano , Tomonori Hoshino , Koji Nakayama , Shogo Takashiba and Naoya Ohara

Infection and Immunity 290 ( 8 ) 5190 - 5202 2015年2月

Attenuation of the phosphatidylinositol 3-Kinase/Akt signaling pathway by porphyromonas gingivalis gingipains RgpA, RgpB, and Kgp

Masaaki Nakayama, Tetsuyoshi Inoue, Mariko Naito, Koji Nakayama, Naoya Ohara

Journal of Biological Chemistry 290 ( 8 ) 5190 - 5202 2015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：American Society for Biochemistry and Molecular Biology Inc.

Background: The significance of gingipains on the PI3K/Akt signaling pathway is poorly understood.Results: The inactivation of PI3K and Akt was induced by P. gingivalis, which was associated with gingipains.Conclusion: Gingipains are critical for suppressing the PI3K/Akt signaling pathway via extracellular proteolysis independent of P. gingivalis invasion. Significance: This study shows the first evidence that the gingipains negatively regulate the PI3K/Akt signaling pathway.

DOI： 10.1074/jbc.M114.591610

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Attenuation of the PI3 kinase/Akt signaling pathway by Porphyromonas gingivalis gingipains RgpA, RgpB, and Kgp 査読

Masaaki Nakayama, Tetsuyoshi Inoue, Mariko Naito, Koji Nakayama and Naoya Ohara

The Journal of Biological Chemistry 290 ( 8 ) 5190 - 5202 2015年1月

Characterization of the tripartite drug efflux pumps of Porphyromonas gingivalis ATCC 33277 査読

Tetsuyoshi Inoue, Masaaki Nakayama, Yuko Taguchi, Konami Kano, Miyuu Ono, Yurika Shimizu, Teruo Kuroda, Naoya Ohara

New Microbiologica 38 ( 1 ) 97 - 103 2015年1月

Role of extracytoplasmic function sigma factors in biofilm formation of Porphyromonas gingivalis 査読国際誌

Satosu Onozawa, Yuichiro Kikuchi, Kazuko Shibayama, Eitoyo Kokubu, Masaaki Nakayama, Tetsuyoshi Inoue, Keisuke Nakano, Yukinaga Shibata, Naoya Ohara, Koji Nakayama, Kazuyuki Ishihara, Toshiyuki Kawakami and Hiromasa Hasegawa

BMC Oral Health 15 4 - 4 2015年1月

Development of a novel plasmid vector pTIO-1 adapted for electrotransformation of Porphyromonas gingivalis 査読

Junpei Tagawa, Tetsuyoshi Inoue, Mariko Naito, Keiko Sato, Tomomi Kuwahara, Masaaki Nakayama, Koji Nakayama, Takashi Yamashiro, Naoya Ohara

JOURNAL OF MICROBIOLOGICAL METHODS 105 174 - 179 2014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：ELSEVIER SCIENCE BV

We report here the construction of a plasmid vector designed for the efficient electrotransformation of the periodontal pathogen Porphyromonas gingivalis. The novel Escherichia coli-Bacteroides/P. gingivalis shuttle vector, designated pTIO-1, is based on the 11.0-kb E. coli-Bacteroides conjugative shuttle vector, pVAL-1 (a pB8-51 derivative). To construct pTIO-1, the pB8-51 origin of replication and erythromycin resistance determinant of pVAL-1 were cloned into the E. coli cloning vector pBluescript II SK(-) and non-functional regions were deleted. pTIO-1 has an almost complete multiple cloning site from pBluescript II SK(-). The size of pTIO-1 is 4.5 kb, which is convenient for routine gene manipulation. pTIO-1 was introduced into P. gingivalis via electroporation, and erythromycin-resistant transformants carrying pTIO-1 were obtained. We characterized the transformation efficiency, copy number, host range, stability, and insert size capacity of pTIO-1. An efficient plasmid electrotransformation of P. gingivalis will facilitate functional analysis and expression of P. gingivalis genes, including the virulence factors of this bacterium. (C) 2014 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.mimet.2014.07.032

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Development of a novel plasmid vector pTIO-1 adapted for electrotransformation of Porphyromonas gingivalis 査読

Junpei Tagawa, Tetsuyoshi Inoue, Mariko Naito, Keiko Sato, Tomomi Kuwahara, Masaaki Nakayama, Koji Nakayama, Takashi Yamashiro, Naoya Ohara

Journal of Microbiological Methods 2014年8月

Hemoglobin receptor protein from Porphyromonas gingivalis induces interleukin-8 production in human gingival epithelial cells through stimulation of the mitogen-activated protein kinase and NF-κB signal transduction pathways. (共著) 査読

Yuki Fujita, Masaaki Nakayama, Mariko Naito, Eiki Yamachika, Tetsuyoshi Inoue, Koji Nakayama, Seiji Iida, and Naoya Ohara

Infection and Immunity 82 ( 1 ) 202 - 211 2014年1月

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