Podocyte programmed cell death in diabetic kidney disease: Molecular mechanisms and therapeutic prospects

• Published in: Biomedicine & pharmacotherapy Vol. 177; p. 117140
• Main Authors: Yang, Haoyu, Sun, Jun, Sun, Aru, Wei, Yu, Xie, Weinan, Xie, Pengfei, Zhang, Lili, Zhao, Linhua, Huang, Yishan
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.08.2024; Elsevier
• Subjects: Apoptosis; Autophagy; Diabetic kidney disease; Podocyte; Programmed cell death; FOXA1; TRAF; TRADD; LncRNA; FOXM1; TNF; NF-κB; UCHL1; PI3P; CIAP1/2; BASP1; TRIM29; DKD; LC3; Rubicon; GPX4; TFEB; IL-8; DHAP; BH4; PCD; PUFA-PL-OH; ROS; CoQ10H2; ULK1; CXCR; LPA; Bcl-2; System Xc; CoQ10; FOXO4; Autophagy; P2X7R; LPS; FSP1; Sp1; NLRP3; RIPK1; Programmed cell death; Bid; Prdx6; GSH; AGE; Diabetic kidney disease; GSDMD; ABCA1; SPAG5; GCH1; MLKL; APE1; RARRES1; Bak; MTOR; TNFR1; Podocyte; WT1; Atg; PE; BAX; Fas; PUFA-PL-OOH; PUFAs; EZH2; H3K27me3; Apoptosis
• ISSN: 0753-3322; 1950-6007; 1950-6007
• DOI: 10.1016/j.biopha.2024.117140

Diabetic kidney disease (DKD) is the primary cause of chronic kidney and end-stage renal disease. Glomerular podocyte loss and death are pathological hallmarks of DKD, and programmed cell death (PCD) in podocytes is crucial in DKD progression. PCD involves apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis. During DKD, PCD in podocytes is severely impacted and primarily characterized by accelerated podocyte apoptosis and suppressed autophagy. These changes lead to a gradual decrease in podocyte numbers, impairing the glomerular filtration barrier function and accelerating DKD progression. However, research on the interactions between the different types of PCD in podocytes is lacking. This review focuses on the novel roles and mechanisms of PCD in the podocytes of patients with DKD. Additionally, we summarize clinical drugs capable of regulating podocyte PCD, present challenges and prospects faced in developing drugs related to podocyte PCD and suggest that future research should further explore the detailed mechanisms of podocyte PCD and interactions among different types of PCD. [Display omitted] •Podocytes are key to glomerular filtration; dysfunction leads to proteinuria and kidney function decline.•Podocyte programmed cell death (PCD) is crucial in diabetic kidney disease (DKD) progression.•Accelerated podocyte apoptosis and suppressed autophagy are key features in DKD.•Some drugs may modulate PCD in DKD podocytes, but more clinical trials are needed.