足细胞自噬与内质网应激在糖尿病肾脏疾病中的作用

The role of podocyte autophagy and endoplasmic reticulum stress in diabetic kidney disease

糖尿病肾脏疾病(DKD)是糖尿病的严重并发症之一,并已成为我国慢性肾衰竭的首要病因。足细胞是一种高度分化的上皮细胞,作为构成肾小球滤过屏障的重要组成部分,其足突融合、消失或裂孔膜蛋白表达下降及足细胞凋亡与脱落均可能导致蛋白尿的发生,并影响DKD的病程进展。自噬是真核细胞降解胞质内蛋白质和细胞器的重要过程,自噬水平的提高有助于减轻足细胞损伤。内质网应激(ERS)是错误折叠的蛋白质在内质网中过度积累,可使细胞进入应激状态,其对细胞损伤的调控可能是双向的。足细胞自噬与ERS受多种信号通路的调节被认为与DKD的发生发展关系密切。本文综述DKD状态下足细胞自噬与ERS的主要信号通路以及足细胞自噬与ERS间的相互影响和作用,提示通过干预足细胞自噬与ERS可以治疗DKD的一些潜在靶点,以期对未来DKD的治疗提供一定帮助。

Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and it has become the leading cause of chronic renal failure in China.Podocytes are highly differentiated epithelial cells and are the important part of the glomerular filtration barrier.Apoptosis and shedding of podocytes,foot process fusion and decreased expression of slit membrane proteins can lead to proteinuria,which in turn affects the progression of DKD.Autophagy is an important process for eukaryotic cells to degrade cytoplasmic proteins and organelles,the increase of autophagy level helps to reduce podocytes damage.Endoplasmic reticulum stress(ERS)is the accumulation of misfolded proteins in cells.It allows the cells into stress state,and may be able to regulate cell damage in both directions.Autophagy and ERS are regulated by multiple signaling pathways and are considered to be closely related to the occurrence and development of DKD.This article explained some pathways and the role of podocyte autophagy and ERS in DKD,and the interaction between podocyte autophagy and ERS,which providing some potential targets for the treatment of DKD by interfering with podocyte autophagy and ERS.