- Diabetes, Obesity and Metabolism
- Short-Chain Fatty Acids Attenuate Renal Fibrosis and Enhance Autophagy of Renal Tubular Cells in Diabetic Mice Through the HDAC2/ULK1 Axis
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Xiaoying Ma, Qiong Wang
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Endocrinol Metab. 2022;37(3):432-443. Published online May 16, 2022
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DOI: https://doi.org/10.3803/EnM.2021.1336
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Abstract
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- Background
This study investigated the effect of short-chain fatty acids (SCFAs) on diabetes in a mouse model.
Methods Autophagy in Akita mice and streptozocin (STZ)-induced diabetic C57BL/6 mice was determined by Western blots and immunohistochemistry (IHC). Western blots, IHC, hematoxylin and eosin staining, Masson staining, periodic acid-Schiff staining, and picrosirius red staining were conducted to detect whether autophagy and renal function improved in Akita mice and STZ-induced diabetic C57BL/6 mice after treatment of SCFAs. Western blots, IHC, and chromatin immunoprecipitation were performed to determine whether SCFAs affected diabetic mice via the histone deacetylase (HDAC2)/unc-51 like autophagy activating kinase 1 (ULK1) axis. Diabetic mice with kidney-specific knockout of HDAC2 were constructed, and IHC, Masson staining, and Western blots were carried out to detect whether the deletion of endogenous HDAC2 contributed to the improvement of autophagy and renal fibrosis in diabetic mice.
Results Reduced autophagy and severe fibrosis were observed in Akita mice and STZ-induced diabetic C57BL/6 mice. Increased autophagy and reduced renal cell fibrosis were found in SCFA-treated Akita diabetic mice and STZ-induced diabetic C57BL/6 mice. Diabetic mice treated with SCFAs had lower HDAC2 expression and more enriched binding of ULK1 promoter sequences to H3K27Ac. Endogenous knockout of HDAC2 caused enhanced autophagy and decreased renal fibrosis in diabetic mice treated with SCFAs.
Conclusion SCFAs enhanced autophagy of renal tubular cells and attenuated renal fibrosis in diabetic mice through the HDAC2/ULK1 axis.
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Citations
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Xin-Hua Jia, Sheng-Yan Wang, Ai-Qin Sun World Journal of Diabetes.2024; 15(3): 475. CrossRef - Epigenetic and post-translational modifications in autophagy: biological functions and therapeutic targets
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KYesoda Aniyan, KrithikaChandrasekar Lakshmi, Anuradha Ganesan Dental Research Journal.2023; 20(1): 73. CrossRef - Luteolin alleviates renal ischemia-reperfusion injury in streptozotocin induced diabetic rats by inhibiting metalloenzymes expression
Rakesh B. Daude, Jigna S. Shah Current Issues in Pharmacy and Medical Sciences.2023; 36(4): 199. CrossRef - Molecular mechanisms of histone deacetylases and inhibitors in renal fibrosis progression
Jiayu Wang, Jiaxing Li, Xin Zhang, Min Zhang, Xiaopeng Hu, Hang Yin Frontiers in Molecular Biosciences.2022;[Epub] CrossRef - Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice
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