- 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
-
Xiaoying Ma, Qiong Wang
-
Endocrinol Metab. 2022;37(3):432-443. Published online May 16, 2022
-
DOI: https://doi.org/10.3803/EnM.2021.1336
-
-
9,152
View
-
175
Download
-
16
Web of Science
-
17
Crossref
-
 Abstract
 PDF PubReader  ePub
- 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.
-
Citations
Citations to this article as recorded by  - Histone deacetylases and their inhibitors in kidney diseases
Yue Zheng, Tie-Ning Zhang, Peng-Hui Hao, Ni Yang, Yue Du
Molecular Therapy.2025;[Epub] CrossRef - Recent advances and potentiality of postbiotics in the food industry: Composition, inactivation methods, current applications in metabolic syndrome, and future trends
Yujie Zhong, Tao Wang, Ruilin Luo, Jiayu Liu, Ruyi Jin, Xiaoli Peng
Critical Reviews in Food Science and Nutrition.2024; 64(17): 5768. CrossRef - NSD1 supports cell growth and regulates autophagy in HPV-negative head and neck squamous cell carcinoma
Iuliia Topchu, Igor Bychkov, Demirkan Gursel, Petr Makhov, Yanis Boumber
Cell Death Discovery.2024;[Epub] CrossRef - Dietary fiber intake and its association with diabetic kidney disease in American adults with diabetes: A cross-sectional study
Xin-Hua Jia, Sheng-Yan Wang, Ai-Qin Sun
World Journal of Diabetes.2024; 15(3): 475. CrossRef - Role of Histone Modifications in Kidney Fibrosis
Shengyu Pan, Tianhui Yuan, Yuqi Xia, Weimin Yu, Xiangjun Zhou, Fan Cheng
Medicina.2024; 60(6): 888. CrossRef - ULK1 as a therapeutic target in kidney diseases: Current perspective
Shruti Shreya, Neha Dagar, Vishwadeep Shelke, Bhupendra Puri, Anil Bhanudas Gaikwad
Expert Opinion on Therapeutic Targets.2024; 28(10): 911. CrossRef - Role of Epigenetic Changes in the Pathophysiology of Diabetic Kidney Disease
Marita Liebisch, Gunter Wolf
Glomerular Diseases.2024; 4(1): 211. CrossRef - N-acetyltransferase 10 regulates UNC-51-like kinase 1 to reduce tubular cell injury and kidney stone formation
Le Wang, Jinjing Huang, Lei Song, Ben Ke
Cytojournal.2024; 21: 68. CrossRef - Epigenetic and post-translational modifications in autophagy: biological functions and therapeutic targets
Feng Shu, Han Xiao, Qiu-Nuo Li, Xiao-Shuai Ren, Zhi-Gang Liu, Bo-Wen Hu, Hong-Sheng Wang, Hao Wang, Guan-Min Jiang
Signal Transduction and Targeted Therapy.2023;[Epub] CrossRef - Mechanisms of Blood–Brain Barrier Protection by Microbiota-Derived Short-Chain Fatty Acids
Ekaterina Fock, Rimma Parnova
Cells.2023; 12(4): 657. CrossRef - The Role of Histone Modifications in the Pathogenesis of Diabetic Kidney Disease
Christodoula Kourtidou, Konstantinos Tziomalos
International Journal of Molecular Sciences.2023; 24(6): 6007. CrossRef - Mechanism of histone deacetylase HDAC2 in FOXO3-mediated trophoblast pyroptosis in preeclampsia
Jia Liu, Weihui Yang
Functional & Integrative Genomics.2023;[Epub] CrossRef - Macrophage polarization induces endothelium-to-myofibroblast transition in chronic allograft dysfunction
Zeping Gui, Xiang Zhang, Qianguang Han, Zhou Hang, Ruoyun Tan, Min Gu, Zijie Wang
Renal Failure.2023;[Epub] CrossRef - Periodic acid–Schiff staining in oral exfoliative cytology of diabetic patients: The odyssey for noninvasive screening – A systematic review and meta-analysis
K. Yesoda Aniyan, Krithika Chandrasekar Lakshmi, Anuradha Ganesan
Dental Research Journal.2023;[Epub] 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
Peipei Wang, Ruixue Guo, Xiwen Bai, Wen Cui, Yiding Zhang, Huangmin Li, Jin Shang, Zhanzheng Zhao
Frontiers in Endocrinology.2022;[Epub] CrossRef
|
KES
