Institute of Nephrology, and Key Laboratory of Prevention and Management of Chronic kidney Disease of Zhanjiang City, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, China.
Cell Death Dis. 2021 Oct 18;12(11):958. doi: 10.1038/s41419-021-04271-w.
Lysosomes are organelles involved in cell metabolism, waste degradation, and cellular material circulation. They play a key role in the maintenance of cellular physiological homeostasis. Compared with the lysosomal content of other organs, that of the kidney is abundant, and lysosomal abnormalities are associated with the occurrence and development of certain renal diseases. Lysosomal structure and function in intrinsic renal cells are impaired in diabetic kidney disease (DKD). Promoting lysosomal biosynthesis and/or restoring lysosomal function can repair damaged podocytes and proximal tubular epithelial cells, and delay the progression of DKD. Lysosomal homeostasis maintenance may be advantageous in alleviating DKD. Here, we systematically reviewed the latest advances in the relationship between lysosomal dyshomeostasis and progression of DKD based on recent literature to further elucidate the mechanism of renal injury in diabetes mellitus and to highlight the application potential of lysosomal homeostasis maintenance as a new prevention and treatment strategy for DKD. However, research on screening effective interventions for lysosomal dyshomeostasis is still in its infancy, and thus should be the focus of future research studies. The screening out of cell-specific lysosomal function regulation targets according to the different stages of DKD, so as to realize the controllable targeted regulation of cell lysosomal function during DKD, is the key to the successful clinical development of this therapeutic strategy.
溶酶体是参与细胞代谢、废物降解和细胞物质循环的细胞器。它们在维持细胞生理内稳态方面起着关键作用。与其他器官的溶酶体含量相比,肾脏的溶酶体含量丰富,溶酶体异常与某些肾脏疾病的发生和发展有关。在糖尿病肾病(DKD)中,内在肾细胞的溶酶体结构和功能受损。促进溶酶体生物合成和/或恢复溶酶体功能可以修复受损的足细胞和近端肾小管上皮细胞,延缓 DKD 的进展。溶酶体稳态的维持可能有利于缓解 DKD。在这里,我们系统地综述了基于最近文献的溶酶体稳态失调与 DKD 进展之间关系的最新进展,以进一步阐明糖尿病中肾脏损伤的机制,并强调维持溶酶体稳态作为 DKD 新的防治策略的应用潜力。然而,针对溶酶体稳态失调的有效干预措施的研究仍处于起步阶段,因此应成为未来研究的重点。根据 DKD 的不同阶段筛选出细胞特异性溶酶体功能调节靶点,从而实现 DKD 期间细胞溶酶体功能的可控靶向调节,是该治疗策略成功临床开发的关键。