Autophagy inhibitor 3-methyladenine attenuates renal injury in streptozotocin-induced diabetic mice
| Autor: | Haiwen Ren, Mengxin Huang, Liwen Ou, Xuan Deng, Xin Wu, Quan Gong, Benju Liu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2024 |
| Předmět: | |
| Zdroj: | Iranian Journal of Basic Medical Sciences, Vol 27, Iss 7, Pp 793-800 (2024) |
| Druh dokumentu: | article |
| ISSN: | 2008-3866 2008-3874 |
| DOI: | 10.22038/ijbms.2024.71378.15518 |
| Popis: | Objective(s): To investigate whether 3-methyladenine (3-MA) can protect the kidney of streptozotocin (STZ) - induced diabetes mice, and explore its possible mechanism. Materials and Methods: STZ was used to induce diabetes in C57BL/6J mice. The mice were divided into normal control group (NC), diabetes group (DM), and diabetes+3-MA intervention group (DM+3-MA). Blood glucose, water consumption, and body weight were recorded weekly. At the end of the 6th week of drug treatment, 24-hour urine was collected. Blood and kidneys were collected for PAS staining to evaluate the degree of renal injury. Sirius red staining was used to assess collagen deposition. Blood urea nitrogen (BUN), serum creatinine, and 24-hour urine albumin were used to evaluate renal function. Western blot was used to detect fibrosis-related protein, inflammatory mediators, high mobility group box 1 (HMGB1)/NF-κB signal pathway molecule, vascular endothelial growth factor (VEGF), and podocin, and immunohistochemistry (IHC) was used to detect the expression and localization of autophagy-related protein and fibronectin.Results: Compared with the kidney of normal control mice, the kidney of diabetes control mice was more pale and hypertrophic. Hyperglycemia induces renal autophagy and activates the HMGB1/NF-κB signal pathway, leading to the increase of inflammatory mediators, extracellular matrix (ECM) deposition, and proteinuria in the kidney. In diabetic mice treated with 3-MA, blood glucose decreased, autophagy and HMGB1/NF-κB signaling pathways in the kidneys were inhibited, and proteinuria, renal hypertrophy, inflammation, and fibrosis were improved. Conclusion: 3-MA can attenuate renal injury in STZ-induced diabetic mice through inhibition of autophagy and HMGB1/NF-κB signaling pathway. |
| Databáze: | Directory of Open Access Journals |
| Externí odkaz: |
|