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  1. 050 医学部, 大学院医学系研究科
  2. 0501 学術論文

TRPC3-GEF-H1 axis mediates pressure overload-induced cardiac fibrosis

http://hdl.handle.net/10091/00021004
http://hdl.handle.net/10091/00021004
f441ea10-e3ac-42c6-b450-324771e9d549
名前 / ファイル ライセンス アクション
srep39383.pdf srep39383.pdf (2.0 MB)
Item type 学術雑誌論文 / Journal Article(1)
公開日 2018-10-31
タイトル
タイトル TRPC3-GEF-H1 axis mediates pressure overload-induced cardiac fibrosis
言語
言語 eng
DOI
関連識別子 https://doi.org/10.1038/srep39383
関連名称 10.1038/srep39383
キーワード
主題 Heart failure, Ion channel signalling
資源タイプ
資源 http://purl.org/coar/resource_type/c_6501
タイプ journal article
著者 Numaga-Tomita, Takuro

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en Numaga-Tomita, Takuro

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Kitajima, Naoyuki

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en Kitajima, Naoyuki

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Kuroda, Takuya

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en Kuroda, Takuya

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Nishimura, Akiyuki

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en Nishimura, Akiyuki

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Miyano, Kei

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en Miyano, Kei

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Yasuda, Satoshi

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en Yasuda, Satoshi

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Kuwahara, Koichiro

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en Kuwahara, Koichiro

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Sato, Yoji

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en Sato, Yoji

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Ide, Tomomi

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Birnbaumer, Lutz

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en Birnbaumer, Lutz

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Sumimoto, Hideki

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en Sumimoto, Hideki

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Mori, Yasuo

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Nishida, Motohiro

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信州大学研究者総覧へのリンク
氏名 Kuwahara, Koichiro
URL http://soar-rd.shinshu-u.ac.jp/profile/ja.HVchWCcp.html
出版者
出版者 NATURE PUBLISHING GROUP
引用
内容記述 SCIENTIFIC REPORTS. 6: 39383(2016)
書誌情報 SCIENTIFIC REPORTS

巻 6, p. 39383, 発行日 2016-12-19
抄録
内容記述 Structural cardiac remodeling, accompanying cytoskeletal reorganization of cardiac cells, is a major clinical outcome of diastolic heart failure. A highly local Ca2+ influx across the plasma membrane has been suggested to code signals to induce Rho GTPase-mediated fibrosis, but it is obscure how the heart specifically decodes the local Ca2+ influx as a cytoskeletal reorganizing signal under the conditions of the rhythmic Ca2+ handling required for pump function. We found that an inhibition of transient receptor potential canonical 3 (TRPC3) channel activity exhibited resistance to Rho-mediated maladaptive fibrosis in pressure-overloaded mouse hearts. Proteomic analysis revealed that microtubule-associated Rho guanine nucleotide exchange factor, GEF-H1, participates in TRPC3-mediated RhoA activation induced by mechanical stress in cardiomyocytes and transforming growth factor (TGF) β stimulation in cardiac fibroblasts. We previously revealed that TRPC3 functionally interacts with microtubule-associated NADPH oxidase (Nox) 2, and inhibition of Nox2 attenuated mechanical stretch-induced GEF-H1 activation in cardiomyocytes. Finally, pharmacological TRPC3 inhibition significantly suppressed fibrotic responses in human cardiomyocytes and cardiac fibroblasts. These results strongly suggest that microtubule-localized TRPC3-GEF-H1 axis mediates fibrotic responses commonly in cardiac myocytes and fibroblasts induced by physico-chemical stimulation
資源タイプ(コンテンツの種類)
ISSN
収録物識別子タイプ PISSN
収録物識別子 2045-2322
PubMed
識別子タイプ PMID
関連識別子 https://www.ncbi.nlm.nih.gov/pubmed/27991560
関連名称 27991560
権利
権利情報 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
出版タイプ
出版タイプ VoR
出版タイプResource http://purl.org/coar/version/c_970fb48d4fbd8a85
WoS
URL http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000389889600001
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