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Review
. 2025 Sep 19:18:13001-13037.
doi: 10.2147/JIR.S545938. eCollection 2025.

Programmed Cell Death in Diabetic Kidney Disease: Mechanisms and Therapeutic Targeting

Shanshan Tang #  1 , Yuting Sun #  2 , Wenjie Sun #  3   4 , Xiaomin Kang  2 , Xuefei Zhao  2 , Linlin Jiang  2 , Qing Gao  2 , Xuedong An  2 , Hangyu Ji  2 , Fengmei Lian  2
Affiliations
Review

Programmed Cell Death in Diabetic Kidney Disease: Mechanisms and Therapeutic Targeting

Shanshan Tang et al. J Inflamm Res. .

Abstract

The escalating incidence and mortality of diabetic kidney disease (DKD) underscore the critical need to elucidate its pathogenesis. Programmed cell death (PCD) plays a dual role in maintaining physiological homeostasis and driving pathological processes in DKD. Accumulating evidence demonstrates that apoptosis, autophagy, pyroptosis, and ferroptosis contribute directly or indirectly to DKD progression via distinct gene-regulated signaling pathways. Recently identified PCD modes (eg, necroptosis, parthanatos) remain poorly characterized in DKD, with emerging evidence suggesting crosstalk between different PCD pathways. This review synthesizes current knowledge on PCD-mediated DKD pathogenesis and PCD-targeted therapies, while highlighting research limitations (eg, unclear PCD interactions, translational gaps). We propose that dissecting the multifaceted roles of PCD in DKD will deepen mechanistic understanding and accelerate the development of novel therapeutics, offering significant scientific and clinical benefits.

Keywords: apoptosis; autophagy; diabetic kidney disease; ferroptosis; programmed cell death; pyroptosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Shows that different factors regulate DKD through apoptosis. By Figdraw.
Figure 2
Figure 2
Shows that different factors regulate DKD through autophagy. By Figdraw.
Figure 3
Figure 3
Shows that different factors regulate DKD through pyroptosis. By Figdraw.
Figure 4
Figure 4
Shows that different factors regulate DKD through ferroptosis. By Figdraw.
See this image and copyright information in PMC

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