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image of Sirt1 Regulates Phenotypic Transformation of Diabetic Cardiac Fibroblasts through Akt/Α-SMA Pathway
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Abstract

Aims:

Cardiac fibrosis causes most pathological alterations of cardiomyopathy in diabetes and heart failure patients. The activation and transformation of cardiac fibroblasts (CFs) are the main pathological mechanisms of cardiac fibrosis. It has been established that Sirtuin1 (Sirt1) plays a protective role in the pathogenesis of cardiovascular disorders. This study aimed to ascertain the Sirt1 effect on the phenotypic transformation of CFs in diabetes and its possible mechanisms.

Methods:

Type 1 diabetes was induced in 6-week-old male mice by subcutaneously injecting 50 mg/kg streptozotocin (STZ, i.p.). Western blotting, collagen staining, and echocardiography were performed to detect protein expression and assess cardiac fibrosis and function . We used high glucose (HG) to culture CFs prior to protein expression measurement .

Results:

Upregulation of Sirt1 expression effectively alleviated the degree of cardiac fibrosis by improving cardiac function in diabetic mice. experiments revealed that HG decreased the protein expression levels of Sirt1, but increased those of type I collagen and alpha-smooth muscle actin (α-SMA), as well as the transdifferentiation of fibroblasts into myofibroblasts. Further studies confirmed that downregulation of Sirt1 expression in the HG environment reduced the protein kinase-B (Akt) phosphorylation, thereby promoting the transdifferentiation of CFs into myofibroblasts coupled with the deterioration of cardiac function.

Conclusion:

Diabetes mellitus leads to downregulation of Sirt1 protein expression in CFs and decreased Akt phosphorylation, which promotes the transdifferentiation of CFs into myofibroblasts, the pathological process of cardiac fibrosis, and mediates the incidence and development of diabetic cardiomyopathy.

© 2025 The Author(s). Published by Bentham Science Publisher.
This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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2025-01-09
2025-01-22

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Sirt1 Regulates Phenotypic Transformation of Diabetic Cardiac Fibroblasts through Akt/Α-SMA Pathway
Bentham Science Publishers , e18761429353519; https://doi.org/10.2174/0118761429353519250106115016
/content/journals/cmp/10.2174/0118761429353519250106115016
/content/journals/cmp/10.2174/0118761429353519250106115016
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  • Article Type:     Research Article
Keywords: Resveratrol ; Protein kinase B (Akt) ; SIRT1 ; Fibroblasts ; Cardiac fibrosis ; Diabetes

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