首页    期刊浏览 2024年11月24日 星期日
登录注册

文章基本信息

  • 标题:TRPC3-GEF-H1 axis mediates pressure overload-induced cardiac fibrosis
  • 本地全文:下载
  • 作者:Takuro Numaga-Tomita ; Naoyuki Kitajima ; Takuya Kuroda
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2016
  • 卷号:6
  • 期号:1
  • DOI:10.1038/srep39383
  • 语种:English
  • 出版社:Springer Nature
  • 摘要:Structural cardiac remodeling, accompanying cytoskeletal reorganization of cardiac cells, is a major clinical outcome of diastolic heart failure. A highly local Ca(2+) 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 Ca(2+) influx as a cytoskeletal reorganizing signal under the conditions of the rhythmic Ca(2+) 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.
国家哲学社会科学文献中心版权所有