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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook 2016     Display Documents



ID: 724016.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook 2016
Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth Factor-beta Signaling Pathway
Authors:Araki, S.; Izumiya, Y.; Rokutanda, T.; Ianni, A.; Hanatani, S.; Kimura, Y.; Onoue, Y.; Senokuchi, T.; Yoshizawa, T.; Yasuda, O.; Koitabashi, N.; Kurabayashi, M.; Braun, T.; Bober, E.; Yamagata, K.; Ogawa, H.
Date of Publication (YYYY-MM-DD):2015-09-22
Title of Journal:Circulation
Volume:132
Issue / Number:12
Start Page:1081
End Page:1093
Audience:Not Specified
Abstract / Description:BACKGROUND: 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. METHODS AND RESULTS: 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(-/-)) 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(-/-) mice. In vitro, Sirt7(-/-) mouse-derived or Sirt7 siRNA-treated cardiac fibroblasts showed reduced transforming growth factor-beta 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-beta receptor I downregulation induced by loss of Sirt7 was blocked by autophagy inhibitor, and interaction of Sirt7 with protein interacting with protein kinase-Calpha was involved in this process. CONCLUSION: Sirt7 maintains transforming growth factor receptor I by modulating autophagy and is involved in the tissue repair process.
Free Keywords:Animals; Autophagy/drug effects; Disease Models, Animal; Fibroblasts/*drug effects/pathology; Heart/*physiology; Hindlimb/blood supply; In Vitro Techniques; Ischemia/physiopathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardial Infarction/physiopathology; Neovascularization, Physiologic/*physiology; RNA, Small Interfering/pharmacology; Regeneration/*physiology; Signal Transduction/*physiology; Sirtuins/deficiency/genetics/*physiology; Transforming Growth Factor beta/*physiology; Wound Healing/physiology; autophagy; fibroblasts; receptors, transforming growth factor beta; sirtuins; wound healing
External Publication Status:published
Document Type:Article
Communicated by:n.n.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:From Departments of Cardiovascular Medicine (S.A., Y.I., T.R., S.H., Y.K., Y.O., H.O.) and Medical Biochemistry (T.S., T.Y., K.Y.), Graduate School of Medical Sciences, Kumamoto University, Japan; Department of Cardiac Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany (A.I., T.B., E.B.); Department of Cardiovascular Clinical and Translational Research, Kumamoto University Hospital, Japan (O.Y.); and Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Maebashi, Japan (N.K., M.K.). izumiya@kumamoto-u.ac.jp.
Identifiers:ISSN:1524-4539 (Electronic) 0009-7322 (Linking) %R 10.1161/CIRCULATIONAHA.114.014821
URL:http://www.ncbi.nlm.nih.gov/pubmed/26202810
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