Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People's Republic of China.
Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA Medical Center, 1459 Laney Walker Blvd, Augusta, GA, 30912, USA.
Cell Mol Life Sci. 2018 Feb;75(4):669-688. doi: 10.1007/s00018-017-2639-1. Epub 2017 Sep 4.
Diabetic kidney disease, a leading cause of end-stage renal disease, has become a serious public health problem worldwide and lacks effective therapies. Autophagy is a highly conserved lysosomal degradation pathway that removes protein aggregates and damaged organelles to maintain cellular homeostasis. As important stress-responsive machinery, autophagy is involved in the pathogenesis of various diseases. Emerging evidence has suggested that dysregulated autophagy may contribute to both glomerular and tubulointerstitial pathologies in kidneys under diabetic conditions. This review summarizes the recent findings regarding the role of autophagy in the pathogenesis of diabetic kidney disease and highlights the regulation of autophagy by the nutrient-sensing pathways and intracellular stress signaling in this disease. The advances in our understanding of autophagy in diabetic kidney disease will facilitate the discovery of a new therapeutic target for the prevention and treatment of this life-threatening diabetes complication.
糖尿病肾病是终末期肾病的主要病因,已成为全球严重的公共卫生问题,且缺乏有效的治疗方法。自噬是一种高度保守的溶酶体降解途径,可清除蛋白质聚集体和受损的细胞器,以维持细胞内稳态。自噬作为重要的应激反应机制,参与了各种疾病的发病机制。新出现的证据表明,在糖尿病条件下,自噬失调可能导致肾小球和肾小管间质病变。本综述总结了自噬在糖尿病肾病发病机制中的作用的最新发现,并强调了营养感应途径和细胞内应激信号对该疾病自噬的调节。我们对糖尿病肾病中自噬的理解的进展将有助于发现预防和治疗这种危及生命的糖尿病并发症的新治疗靶点。