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Endothelial SIRT3 regulates myofibroblast metabolic shifts in diabetic kidneys
- Source :
- iScience, Vol 24, Iss 5, Pp 102390-(2021), iScience
- Publication Year :
- 2020
- Publisher :
- Cold Spring Harbor Laboratory, 2020.
-
Abstract
- Summary 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 TGFβ/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.<br />Graphical abstract<br />Highlights • Endothelial SIRT3 protects against renal fibrosis in diabetes • Endothelial SIRT3 regulates mesenchymal metabolic shifts • Amelioration of endothelial SIRT3 could be a potential therapeutic approach • Targeting defective metabolism offers new therapeutics against kidney diseases<br />Biological Sciences ; Cell Biology ; Functional Aspects of Cell Biology
- Subjects :
- 0301 basic medicine
SIRT3
Science
Regulator
Renal function
Context (language use)
02 engineering and technology
Article
03 medical and health sciences
Fibrosis
Diabetes mellitus
Renal fibrosis
medicine
Kidney
Functional Aspects of Cell Biology
Multidisciplinary
Chemistry
business.industry
Mesenchymal stem cell
Cell Biology
Biological Sciences
021001 nanoscience & nanotechnology
medicine.disease
Cell biology
Endothelial stem cell
030104 developmental biology
medicine.anatomical_structure
Cancer research
0210 nano-technology
business
Myofibroblast
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- iScience, Vol 24, Iss 5, Pp 102390-(2021), iScience
- Accession number :
- edsair.doi.dedup.....2e4c6e7ae85ba7b2dabd62b6b2f38322