title: Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth Factor-β Signaling Pathway.
abstract: 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.
  
  
  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-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.
  
  
  CONCLUSIONS
  Sirt7 maintains transforming growth factor receptor I by modulating autophagy and is involved in the tissue repair process.
authors.affiliation: 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.).
authors.forename: Satoshi
authors.initials: S
authors.lastname: Araki
authors.affiliation: 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.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Izumiya
authors.affiliation: 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.).
authors.forename: Taku
authors.initials: T
authors.lastname: Rokutanda
authors.affiliation: 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.).
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ianni
authors.affiliation: 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.).
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Hanatani
authors.affiliation: 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.).
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: 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.).
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Onoue
authors.affiliation: 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.).
authors.forename: Takafumi
authors.initials: T
authors.lastname: Senokuchi
authors.affiliation: 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.).
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yoshizawa
authors.affiliation: 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.).
authors.forename: Osamu
authors.initials: O
authors.lastname: Yasuda
authors.affiliation: 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.).
authors.forename: Norimichi
authors.initials: N
authors.lastname: Koitabashi
authors.affiliation: 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.).
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kurabayashi
authors.affiliation: 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.).
authors.forename: Thomas
authors.initials: T
authors.lastname: Braun
authors.affiliation: 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.).
authors.forename: Eva
authors.initials: E
authors.lastname: Bober
authors.affiliation: 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.).
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamagata
authors.affiliation: 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.).
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D006321:Heart / Q000502:physiology*; D006614:Hindlimb / Q000098:blood supply; D066298:In Vitro Techniques; D007511:Ischemia / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D037761:Sirtuins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology
chemical_list: D034741:RNA, Small Interfering; C539736:Sirt7 protein, mouse; D016212:Transforming Growth Factor beta; D037761:Sirtuins
keywords: autophagy; fibroblasts; receptors, transforming growth factor beta; sirtuins; wound healing