Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth Factor-β Signaling Pathway. Issue 12 (22nd September 2015)

• Record Type: Journal Article
• Authors: Araki, Satoshi; Izumiya, Yasuhiro; Rokutanda, Taku; Ianni, Alessandro; Hanatani, Shinsuke; Kimura, Yuichi; Onoue, Yoshiro; Senokuchi, Takafumi; Yoshizawa, Tatsuya; Yasuda, Osamu; Koitabashi, Norimichi; Kurabayashi, Masahiko; Braun, Thomas; Bober, Eva; Yamagata, Kazuya; Ogawa, Hisao
• Is Part Of: Circulation. Volume 132:Issue 12(2015)
• Publication Date: 2015-09-22
• Subjects: Blood -- Circulation -- Periodicals; Cardiovascular system -- Periodicals; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; 616.1
• DOI: 10.1161/CIRCULATIONAHA.114.014821
• Languages: English
• ISSNs: 0009-7322

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Background—</title> <p>Sirt7, 1 of the 7 members of the mammalian sirtuin family, promotes oncogenic transformation. Tumor growth and metastasis require fibrotic and angiogenic responses. Here, we investigated the role of Sirt7 in cardiovascular tissue repair process.</p> </sec> <sec> <title>Methods and Results—</title> <p>In wild-type mice, Sirt7 expression increased in response to acute cardiovascular injury, including myocardial infarction and hind-limb ischemia, particularly at the active wound healing site. Compared with wild-type mice, homozygous Sirt7-deficient (Sirt7<sup>−/−</sup>) mice showed susceptibility to cardiac rupture after myocardial infarction, delayed blood flow recovery after hind-limb ischemia, and impaired wound healing after skin injury. Histological analysis showed reduced fibrosis, fibroblast differentiation, and inflammatory cell infiltration in the border zone of infarction in Sirt7<sup>−/−</sup> mice. In vitro, Sirt7<sup>−/−</sup> mouse–derived or Sirt7 siRNA–treated cardiac fibroblasts showed reduced transforming growth factor-β signal activation and low expression levels of fibrosis-related genes compared with wild-type mice–derived or control siRNA–treated cells. These changes were accompanied by reduction in transforming growth factor receptor I protein. Loss of Sirt7 activated autophagy in cardiac fibroblasts. Transforming growth factor-β receptor I downregulation induced by loss of Sirt7 was blocked by autophagy inhibitor, and interaction of Sirt7 with protein interacting with protein kinase-Cα was involved in this process.</p> </sec> <sec> <title>Conclusion—</title> <p>Sirt7 maintains transforming growth factor receptor I by modulating autophagy and is involved in the tissue repair process.</p> </sec> </abstract>