首页    期刊浏览 2022年06月28日 星期二
登录注册

文章基本信息

  • 标题:Acute Hyperthermia Inhibits TGF-β1-induced Cardiac Fibroblast Activation via Suppression of Akt Signaling
  • 本地全文:下载
  • 作者:Masatoshi Narikawa ; Masanari Umemura ; Ryo Tanaka
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2018
  • 卷号:8
  • 期号:1
  • 页码:6277
  • DOI:10.1038/s41598-018-24749-6
  • 语种:English
  • 出版社:Springer Nature
  • 摘要:Transforming growth factor-β1 (TGF-β1) induces phenotypic changes in fibroblasts to become myofibroblasts with increased production of extracellular matrix (ECM) components and cytokines. It is also known that excessive activation of myofibroblasts accelerates cardiac fibrosis, remodeling, and thus cardiac dysfunction. However, no effective therapy has been established to prevent this process although recent clinical studies have demonstrated the effectiveness of hyperthermia in cardiac dysfunction. The aim of this study was to examine the molecular mechanism of hyperthermia on TGF-β1-mediated phenotypic changes in cardiac fibroblasts. TGF-β1 increased the expression of IL-6, α-smooth muscle actin (α-SMA), and collagen in human cardiac fibroblasts (HCFs). Hyperthermia (42 °C) significantly prevented these changes, i.e., increases in IL-6, α-SMA, and collagen, as induced by TGF-β1 in a time-dependent manner. Immunoblotting showed that hyperthermia decreased Akt/S6K signaling, but did not affect Smad2 and Smad3 signaling. Pharmacological inhibition of Akt signaling mimicked these effects of hyperthermia. Furthermore, hyperthermia treatment prevented cardiac fibrosis in Ang II infusion mice model. Putting together, our findings suggest that hyperthermia directly inhibits TGF-β-mediated activation of HCFs via suppressing Akt/S6K signaling.
国家哲学社会科学文献中心版权所有