Zhou Jingbo, Zhang Shu, Sun Xinyi, Lou Yan, Bao Jinjing, Yu Jiangyi
Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu, China.
Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu, China.
J Pharmacol Sci. 2021 May;146(1):10-20. doi: 10.1016/j.jphs.2021.02.005. Epub 2021 Feb 13.
Diabetic nephropathy is a serious complication of diabetes. Hyperoside has been widely reported to ameliorate diabetes-associated disease. The current study is designed to explore the mechanism of hyperoside in diabetic nephropathy. In the present study, high glucose was used to treat podocytes. Diabetic nephropathy mice models were established by high-fat feeding followed by multiple low dose injections of streptozocin. Western blot analysis was conducted for detection of extracellular matrix accumulation, inflammatory response and cell apoptosis. We found out that hyperoside improved high glucose-induced cell injury. Additionally, hyperoside prevented mice with diabetic nephropathy from diabetic symptoms and renal dysfunction. Mechanistically, hyperoside inhibited the mRNA and protein expression of APC. MiR-499-5p was found to be an upstream negative mediator of APC, and hyperoside induced the upregulation of miR-499-5p. MiR-499-5p bound with the 3' untranslated region of APC to inhibit its expression. Finally, rescue assays revealed that the suppressive effects of miR-499-5p overexpression on renal dysfunction were rescued by upregulation of APC in mice with diabetic nephropathy. In conclusion, these findings indicated that hyperoside ameliorates diabetic nephropathy via targeting the miR-499-5p/APC axis, suggesting that hyperoside may offer a potential tactic for diabetic nephropathy treatment.
糖尿病肾病是糖尿病的一种严重并发症。大量报道显示金丝桃苷可改善糖尿病相关疾病。本研究旨在探讨金丝桃苷治疗糖尿病肾病的机制。在本研究中，采用高糖处理足细胞。通过高脂喂养联合多次低剂量注射链脲佐菌素建立糖尿病肾病小鼠模型。采用蛋白质免疫印迹分析检测细胞外基质积聚、炎症反应和细胞凋亡情况。我们发现金丝桃苷可改善高糖诱导的细胞损伤。此外，金丝桃苷可使糖尿病肾病小鼠的糖尿病症状和肾功能障碍得到改善。机制上，金丝桃苷可抑制APC的mRNA和蛋白表达。发现miR-499-5p是APC的上游负向调节因子，金丝桃苷可诱导miR-499-5p表达上调。miR-499-5p与APC的3'非翻译区结合以抑制其表达。最后，挽救实验显示，在糖尿病肾病小鼠中，上调APC可逆转miR-499-5p过表达对肾功能障碍的抑制作用。总之，这些研究结果表明金丝桃苷通过靶向miR-499-5p/APC轴改善糖尿病肾病，提示金丝桃苷可能为糖尿病肾病的治疗提供一种潜在策略。
