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Endothelial SIRT3 regulates myofibroblast metabolic shifts in diabetic kidneys.
Srivastava, Swayam Prakash; Li, Jinpeng; Takagaki, Yuta; Kitada, Munehiro; Goodwin, Julie E; Kanasaki, Keizo; Koya, Daisuke.
Afiliación
  • Srivastava SP; Department of Diabetology & Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
  • Li J; Department of Pediatrics (Nephrology) Yale University School of Medicine, New Haven, CT 06520, USA.
  • Takagaki Y; Vascular Biology and Therapeutics Program, Yale University School of Medicine New Haven, CT 06520, USA.
  • Kitada M; Department of Diabetology & Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
  • Goodwin JE; Department of Diabetology & Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
  • Kanasaki K; Department of Diabetology & Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
  • Koya D; Department of Anticipatory Molecular Food Science and Technology, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
iScience ; 24(5): 102390, 2021 May 21.
Article en En | MEDLINE | ID: mdl-33981977
Defects in endothelial cells cause deterioration in kidney function and structure. Here, we found that endothelial SIRT3 regulates metabolic reprogramming and fibrogenesis in the kidneys of diabetic mice. By analyzing, gain of function of the SIRT3 gene by overexpression in a fibrotic mouse strain conferred disease resistance against diabetic kidney fibrosis, whereas its loss of function in endothelial cells exacerbated the levels of diabetic kidney fibrosis. Regulation of endothelial cell SIRT3 on fibrogenic processes was due to tight control over the defective central metabolism and linked activation of endothelial-to-mesenchymal transition (EndMT). SIRT3 deficiency in endothelial cells stimulated the TGFß/Smad3-dependent mesenchymal transformations in renal tubular epithelial cells. These data demonstrate that SIRT3 regulates defective metabolism and EndMT-mediated activation of the fibrogenic pathways in the diabetic kidneys. Together, our findings show that endothelial SIRT3 is a fundamental regulator of defective metabolism regulating health and disease processes in the kidney.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos