School of Basic Medical Sciences & Forensic Medicine, Hangzhou Medical College, Hangzhou, China.
Front Endocrinol (Lausanne). 2023 Mar 20;14:1139444. doi: 10.3389/fendo.2023.1139444. eCollection 2023.
Diabetic nephropathy (DN), the leading cause of end-stage renal disease, is the most significant microvascular complication of diabetes and poses a severe public health concern due to a lack of effective clinical treatments. Autophagy is a lysosomal process that degrades damaged proteins and organelles to preserve cellular homeostasis. Emerging studies have shown that disorder in autophagy results in the accumulation of damaged proteins and organelles in diabetic renal cells and promotes the development of DN. Autophagy is regulated by nutrient-sensing pathways including AMPK, mTOR, and Sirt1, and several intracellular stress signaling pathways such as oxidative stress and endoplasmic reticulum stress. An abnormal nutritional status and excess cellular stresses caused by diabetes-related metabolic disorders disturb the autophagic flux, leading to cellular dysfunction and DN. Here, we summarized the role of autophagy in DN focusing on signaling pathways to modulate autophagy and therapeutic interferences of autophagy in DN.
糖尿病肾病(DN)是终末期肾病的主要病因,也是糖尿病最严重的微血管并发症,由于缺乏有效的临床治疗方法,因此成为严重的公共卫生问题。自噬是溶酶体降解途径,可降解受损蛋白和细胞器,以维持细胞内稳态。新出现的研究表明,自噬失调会导致糖尿病肾细胞中受损蛋白和细胞器的积累,并促进 DN 的发展。自噬受包括 AMPK、mTOR 和 Sirt1 在内的营养感应途径以及氧化应激和内质网应激等几种细胞内应激信号通路调节。由糖尿病相关代谢紊乱引起的异常营养状态和过多细胞应激会扰乱自噬流,导致细胞功能障碍和 DN。在这里,我们总结了自噬在 DN 中的作用,重点介绍了调节自噬的信号通路以及自噬在 DN 中的治疗干预。