Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth Factor-ß Signaling Pathway.
Circulation
; 132(12): 1081-93, 2015 Sep 22.
Article
em En
| MEDLINE
| ID: mdl-26202810
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. METHODS ANDRESULTS:
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-ß 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-ß 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.CONCLUSION:
Sirt7 maintains transforming growth factor receptor I by modulating autophagy and is involved in the tissue repair process.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Regeneração
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Transdução de Sinais
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Fator de Crescimento Transformador beta
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Neovascularização Fisiológica
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Sirtuínas
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Fibroblastos
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Coração
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Circulation
Ano de publicação:
2015
Tipo de documento:
Article