Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
Changchun University of Chinese Medicine, Changchun 130117, China.
Biomed Pharmacother. 2024 Aug;177:117140. doi: 10.1016/j.biopha.2024.117140. Epub 2024 Jul 16.
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.
糖尿病肾病（DKD）是导致慢性肾脏疾病和终末期肾病的主要原因。肾小球足细胞的丧失和死亡是 DKD 的病理特征，而足细胞中的程序性细胞死亡（PCD）在 DKD 的进展中至关重要。PCD 涉及细胞凋亡、自噬、铁死亡、细胞焦亡和坏死性凋亡。在 DKD 中，足细胞中的 PCD 受到严重影响，主要表现为足细胞凋亡加速和自噬抑制。这些变化导致足细胞数量逐渐减少，损害肾小球滤过屏障功能，并加速 DKD 的进展。然而，关于足细胞中不同类型 PCD 之间相互作用的研究还很缺乏。本综述重点关注 DKD 患者足细胞中 PCD 的新作用和机制。此外，我们总结了能够调节足细胞 PCD 的临床药物，提出了在开发与足细胞 PCD 相关药物方面面临的挑战和前景，并建议未来的研究应进一步探索足细胞 PCD 的详细机制以及不同类型 PCD 之间的相互作用。
