足细胞损伤机制及其治疗糖尿病肾病潜在策略的研究进展

doi:10.13481/j.1671-587X.20250531

Abstract

Abstract:

Diabetic nephropathy （DN） is a significant causative factor of end-stage renal disease globally， and its pathogenesis involves dysregulation of multiple cellular and hormonal pathways. Podocytes play crucial roles in the process of DN， with the extent of podocyte injury closely associated with key pathological manifestations of renal damage， such as proteinuria， glomerular filtration rate， and glomerulosclerosis. However， due to the complexity and interplay of mechanisms contributing to podocyte injury， such as oxidative stress， abnormal lipid metabolism， and mitochondrial damage， the precise mechanisms underlying podocyte injury remain incompletely understood. This review integrated the latest research findings from both domestic and international studies on the core mechanisms of podocyte injury in DN. Furthermore， this article summarized the implications of these mechanisms for DN treatment， particularly focusing on potential therapeutic targets and the development of related pharmacological interventions derived from targeting podocyte injury pathways， so as to provide a theoretical foundation for the development of clinical therapeutic strategies for DN.

Key words: Podocyte, Injury mechanism, Diabetic nephropathy, Therapeutic target, Renin-angiotensin-aldosterone system, Mitochondrial damage

CLC Number:

R329.2

Xun LU,Chengxin MA,Jianan YANG,Xinxin GUO,Xiaobei XIE,Binghai ZHAO,Hongzhi LI. Research progress in mechanism of podocyte injury and its potential therapeutic strategies for diabetic nephropathy[J].Journal of Jilin University(Medicine Edition), 2025, 51(5): 1415-1422.

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References 50

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Target site	Expression	Pathway	Mechanism	Reference
Klotho	↑	Nrf2/ARE	Anti-oxidation，anti-apoptosis	[21]
USP15	↓	Nrf2/ARE	Anti-oxidation，anti-inflammatory	[22]
GSK-3β	↓	Nrf2/ARE	Anti-oxidation	[23]
TRIM32	↓	AKT/GSK-3β/Nrf2	Anti-oxidation，anti-apoptosis	[24]
REDD1	↓	AKT/GSK-3β/Nrf2	Anti-oxidation，anti-apoptosis	[25]
LncRNA 1500026H17Rik	↓	miR-205-5p/EGR1	Anti-oxidation,anti-fibrosis,anti-inflammation	[26]
LncRNA SNHG5	↓	miR-26a-5p/TRPC6	Anti-oxidation，anti-apoptosis	[27]
FOXO3a	↓	AOPPs/ROS/mTOR	Anti-oxidation，anti-apoptosis	[28]
Rab11	↓	Ang Ⅱ/Rab11/LDLR	Reduce lipid accumulation	[32]
JAML	↓	SIRT1-AMPK/SREBP1	Reduce lipid accumulation	[10]
GPR43	↓	ERK/EGFR1	Reduce lipid accumulation	[33]
STING	↓	mtDNA-cGAS-STING	Reduce lipid accumulation	[34]
CCDC 92	↓	ABCA1	Reduce lipid accumulation	[35]
CD36	↓	CD36/ROS/TRPC6	Anti-oxidation, reduce lipid accumulation	[36]
GPD1	↓	Ang Ⅱ/DHAP/G-3-P	Reduce lipid accumulation	[39]
SIRT6	↑	Ang Ⅱ/ROCK1/DRP1	Reduce mitochondrial dynamic imbalance	[40]
SOCE	↓	Ang Ⅱ/IP₃， DAG/TRPC6	Alleviate mitochondrial respiratory dysfunction	[41]
LncRNA 585189	↓	hnRNA A1/SIRT1	Alleviate mitochondrial dysfunction	[42]
PKM2	↑	HIF-α/VEGF	Anti-oxidation, improve mitochondrial function	[43]
AKAP1-DRP1	↓	MAMs/AKAP1-DRP1	Inhibit excessive mitochondrial division	[44]
AT2R	↑	RAS/AT1R, NOS	Anti-apoptosis,anti-fibrosis,anti-inflammation	[47]
Ang Ⅱ	↓	PI3K/AKT/NF?κB	Anti-oxidation， anti-apoptosis	[48]

Research progress in mechanism of podocyte injury and its potential therapeutic strategies for diabetic nephropathy

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