P2Y6 receptor-Gα12/13 signalling in cardiomyocytes triggers pressure overload-induced cardiac fibrosis

Motohiro Nishida, Yoji Sato, Aya Uemura, Yusuke Narita, Hidetoshi Tozaki-Saitoh, Michio Nakaya, Tomomi Ide, Kazuhiro Suzuki, Kazuhide Inoue, Taku Nagao, Hitoshi Kurose

研究成果: ジャーナルへの寄稿学術誌査読

159 被引用数 (Scopus)


Cardiac fibrosis, characterized by excessive deposition of extracellular matrix proteins, is one of the causes of heart failure, and it contributes to the impairment of cardiac function. Fibrosis of various tissues, including the heart, is believed to be regulated by the signalling pathway of angiotensin II (Ang II) and transforming growth factor (TGF)-β. Transgenic expression of inhibitory polypeptides of the heterotrimeric G12 family G protein (Gα12/13) in cardiomyocytes suppressed pressure overload-induced fibrosis without affecting hypertrophy. The expression of fibrogenic genes (TGF-β, connective tissue growth factor, and periostin) and Ang-converting enzyme (ACE) was suppressed by the functional inhibition of Gα12/13. The expression of these fibrogenic genes through Gα12/13 by mechanical stretch was initiated by ATP and UDP released from cardiac myocytes through pannexin hemichannels. Inhibition of G-protein-coupled P2Y6 receptors suppressed the expression of ACE, fibrogenic genes, and cardiac fibrosis. These results indicate that activation of Gα12/13 in cardiomyocytes by the extracellular nucleotides-stimulated P2Y6 receptor triggers fibrosis in pressure overload-induced cardiac fibrosis, which works as an upstream mediator of the signalling pathway between Ang II and TGF-β.

ジャーナルEMBO Journal
出版ステータス出版済み - 12月 3 2008

!!!All Science Journal Classification (ASJC) codes

  • 神経科学(全般)
  • 分子生物学
  • 生化学、遺伝学、分子生物学(全般)
  • 免疫学および微生物学(全般)


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