Autophagy inhibitor 3-methyladenine attenuates renal injury in streptozotocin-induced diabetic mice

作者全名：Ren, Haiwen; Huang, Mengxin; Ou, Liwen; Deng, Xuan; Wu, Xin; Gong, Quan; Liu, Benju

作者地址：[Ren, Haiwen] Chongqing Med Univ, Dept Clin Lab, Bishan Hosp, Chongqing 402760, Peoples R China; [Ren, Haiwen; Huang, Mengxin; Ou, Liwen; Deng, Xuan; Wu, Xin] Yangtze Univ, Hlth Sci Ctr, Jingzhou 434023, Peoples R China; [Gong, Quan] Yangtze Univ, Med Sch, Dept Immunol, Jingzhou 434023, Peoples R China; [Gong, Quan] Yangtze Univ, Clin Mol Immunol Ctr, Med Sch, Jingzhou 434023, Peoples R China; [Liu, Benju] Yangtze Univ, Med Sch, Dept Human Anat, Jingzhou 434023, Peoples R China

通信作者：Gong, Q (通讯作者)，Yangtze Univ, Med Sch, Dept Immunol, Jingzhou 434023, Peoples R China.; Gong, Q (通讯作者)，Yangtze Univ, Clin Mol Immunol Ctr, Med Sch, Jingzhou 434023, Peoples R China.; Liu, BJ (通讯作者)，Yangtze Univ, Med Sch, Dept Human Anat, Jingzhou 434023, Peoples R China.

来源：IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001223071800004

JCR分区：Q3

影响因子：2.1

年份：2024

卷号：27

期号：7

开始页：793

结束页：800

文献类型：Article

关键词：3-Methyladenine; Autophagy; Diabetes; Diabetic nephropathy; HMGB1/NF-kappa B signaling-pathway

摘要：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-KB 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 -KB 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-KB 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-KB signaling pathway.

基金机构：National Natural Science Foundation of China [82270893]; Joint Fund of Health Committee of Hubei Province

基金资助正文：<B>Acknowledgment</B> This study was supported by the National Natural Science Foundation of China (No.82270893) and the Joint Fund of Health Committee of Hubei Province (No.WJ2019-16) .