溶酶体与肾固有细胞病理生理研究进展

Progress in research on lysosome and pathophysiology of intrinsic renal cells

溶酶体是一种富含酸性水解酶的细胞器,是胞内主要的降解工厂,参与物质分泌、质膜修复、细胞信号传导和能量代谢等过程,其功能异常与多种疾病相关。近年发现,肾固有细胞溶酶体功能障碍参与慢性肾病的发生发展:溶酶体功能障碍可导致足细胞自噬受阻,诱发足细胞的转分化和损伤;近端小管上皮细胞溶酶体损伤可通过诱导氧化应激诱导其凋亡;系膜细胞溶酶体损伤可导致其Ⅰ型胶原蛋白降解减少;溶酶体组织蛋白酶-S及α-半乳糖苷酶-A表达异常与肾内皮细胞功能障碍密切相关。综上,溶酶体功能障碍与肾固有细胞的病理生理过程密切相关,阐明溶酶体在肾固有细胞的作用,有望为明确慢性肾病肾固有细胞的损伤机制提供新思路。

The lysosome,an organelle rich in acidic hydrolase,is the main degradation organelle in the cell and is involved in cell processes such as secretion,plasma membrane repair,cell signaling,and energy metabolism.Lysosomal dysfunction may be related to the development of various diseases.In recent years,studies have shown that lysosomal dysfunction may be involved in the development of chronic kidney disease(CKD):lysosomal dysfunction of podocytes interrupts autophagy,inducing transdifferentiation and damage of podocytes.Lysosomal damage mediates apoptosis in proximal tubule epithelial cells via oxidative stress.Lysosomal damage leads to reduced degradation of type I collagen in mesangial cells.Renal endothelial cell dysfunction is closely related to the abnormal expression of lysosomal cathepsin-S andα-galactosidase-A.In summary,lysosomal dysfunction is closely linked to the pathology of intrinsic renal cells.Elucidation of the function of the lysosome in intrinsic renal cells should provide new ideas for clarifying the mechanism of intrinsic renal cell damage in chronic kidney disease.