Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang avenue number 1277, Wuhan, 430022, China.
J Nephrol. 2022 Jul;35(6):1571-1584. doi: 10.1007/s40620-022-01269-1. Epub 2022 Feb 24.
Diabetic kidney disease (DKD) accounts for a large proportion of end-stage renal diseases that require renal replacement therapies including dialysis and transplantation. Therefore, it is critical to understand the occurrence and development of DKD. Podocytes are mainly injured during the development of DKD, ultimately leading to their extensive death and loss. In turn, the injury and death of glomerular podocytes are also the main culprits of DKD. This review introduces the characteristics of podocytes and summarizes the modes of their death in DKD, including apoptosis, autophagy, mitotic catastrophe (MC), anoikis, necroptosis, and pyroptosis. Apoptosis is characterized by nuclear condensation and the formation of apoptotic bodies, and it exerts a different effect from autophagy in mediating DKD-induced podocyte loss. MC mediates a faulty mitotic process while anoikis separates podocytes from the basement membrane. Moreover, pyroptosis activates inflammatory factors to aggravate podocyte injuries whilst necroptosis drives signaling cascades, such as receptor-interacting protein kinases 1 and 3 and mixed lineage kinase domain-like, ultimately promoting the death of podocytes. In conclusion, a thorough knowledge of the modes of podocyte death in DKD can help us understand the development of DKD and lay the foundation for strategies in DKD disease therapy.
糖尿病肾病（DKD）占需要肾脏替代治疗（包括透析和移植）的终末期肾病的很大比例。因此，了解 DKD 的发生和发展至关重要。在 DKD 的发展过程中，主要是足细胞受到损伤，最终导致其广泛死亡和丧失。反过来，肾小球足细胞的损伤和死亡也是 DKD 的主要罪魁祸首。本综述介绍了足细胞的特征，并总结了 DKD 中足细胞死亡的方式，包括细胞凋亡、自噬、有丝分裂灾难（MC）、失巢凋亡、坏死性凋亡和焦亡。细胞凋亡的特征是核浓缩和凋亡小体的形成，它在介导 DKD 诱导的足细胞丢失方面与自噬的作用不同。MC 介导有缺陷的有丝分裂过程，而失巢凋亡使足细胞与基底膜分离。此外，焦亡激活炎症因子加重足细胞损伤，而坏死性凋亡驱动信号级联反应，如受体相互作用蛋白激酶 1 和 3 以及混合谱系激酶结构域样蛋白，最终促进足细胞死亡。总之，深入了解 DKD 中足细胞死亡的方式有助于我们了解 DKD 的发展，并为 DKD 疾病治疗策略奠定基础。
