Research Progress on the Role and Mechanism of Pyroptosis in Diabetic Kidney Disease

Zhenqin RAN; Zehui LIU; Rong YANG; Zizhou WANG; Lixin CHEN; Rui HAN

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Zhenqin RAN, Zehui LIU, Rong YANG, Zizhou WANG, Lixin CHEN, Rui HAN. Research Progress on the Role and Mechanism of Pyroptosis in Diabetic Kidney Disease[J]. Journal of Kunming Medical University.

Citation:

Zhenqin RAN, Zehui LIU, Rong YANG, Zizhou WANG, Lixin CHEN, Rui HAN. Research Progress on the Role and Mechanism of Pyroptosis in Diabetic Kidney Disease[J]. Journal of Kunming Medical University.

Zhenqin RAN, Zehui LIU, Rong YANG, Zizhou WANG, Lixin CHEN, Rui HAN. Research Progress on the Role and Mechanism of Pyroptosis in Diabetic Kidney Disease[J]. Journal of Kunming Medical University.

Citation:

Zhenqin RAN, Zehui LIU, Rong YANG, Zizhou WANG, Lixin CHEN, Rui HAN. Research Progress on the Role and Mechanism of Pyroptosis in Diabetic Kidney Disease[J]. Journal of Kunming Medical University.

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Research Progress on the Role and Mechanism of Pyroptosis in Diabetic Kidney Disease

Department of International Medicine，The First Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650032，China

Received Date: 2025-11-17
Available Online: 2026-01-06

Abstract

Abstract

Diabetic kidney disease （DKD） is one of the most common microvascular complications of diabetes mellitus, and it is categorized as a sterile inflammatory disease. Pyroptosis is an inflammatory form of programmed cell death mediated by inflammasomes and the cysteine-aspartic acid protease （Caspase） family, which has been demonstrated to play a crucial role in the pathogenesis and progression of DKD in recent years. Stimuli such as hyperglycemia can induce pyroptosis in intrinsic renal cells by activating the NLRP3 inflammasome and related signaling pathways, which further amplifies local inflammatory responses, promotes the process of renal fibrosis, and ultimately leads to progressive deterioration of renal function. This review systematically summarized the molecular mechanisms of pyroptosis and the research progress of pyroptosis in DKD, in order to explore potential intervention strategies targeting the pyroptosis pathway, and provide new theoretical basis and therapeutic ideas for the prevention and treatment of DKD.
- Pyroptosis,
- Diabetic kidney disease,
- Renal fibrosis,
- Research progress

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References(50)

References

[1]	Joumaa J P, Raffoul A, Sarkis C, et al. Mechanisms, biomarkers, and treatment approaches for diabetic kidney disease: Current insights and future perspectives[J]. J Clin Med, 2025, 14(3): 727.
[2]	He Y, Wang X, Li L, et al. Global, regional, and national prevalence of chronic type 2 diabetic kidney disease from 1990 to 2021: A trend and health inequality analyses based on the global burden of disease study 2021[J]. J Diabetes, 2025, 17(5): e70098. doi: 10.1111/1753-0407.70098
[3]	Zhang H, Wang K, Zhao H, et al. Diabetic kidney disease: from pathogenesis to multimodal therapy-current evidence and future directions[J]. Front Med, 2025, 12: 1631053.
[4]	Efiong E E, Maedler K, Effa E, et al. Decoding diabetic kidney disease: a comprehensive review of interconnected pathways, molecular mediators, and therapeutic insights[J]. Diabetol Metab Syndr, 2025, 17(1): 192.
[5]	Fang B, Huang W, Du S, et al. The inflammatory cell death in diabetic kidney disease: Integrating multifactorial mechanisms into novel therapeutics[J]. Int J Mol Sci, 2025, 26(22): 11033. doi: 10.3390/ijms262211033
[6]	Chen Y, Chen R, Ji X, et al. NLRP3 inflammasome-mediated pyroptosis in diabetic nephropathy: pathogenic mechanisms and therapeutic Targets[J]. J Inflamm Res, 2025, 18: 8399-8418.
[7]	Zheng X, Wan J, Tan G. The mechanisms of NLRP3 inflammasome/pyroptosis activation and their role in diabetic retinopathy[J]. Front Immunol, 2023, 14: 1151185. doi: 10.3389/fimmu.2023.1151185
[8]	Vasudevan S O, Behl B, Rathinam V A. Pyroptosis-induced inflammation and tissue damage[J]. Semin Immunol, 2023, 69: 101781. doi: 10.1016/j.smim.2023.101781
[9]	Wright S S, Vasudevan S O, Rathinam V A. Mechanisms and consequences of noncanonical inflammasome-mediated pyroptosis[J]. J Mol Biol, 2022, 434(4): 167245. doi: 10.1016/j.jmb.2021.167245
[10]	Du T, Gao J, Li P, et al. Pyroptosis, metabolism, and tumor immune microenvironment[J]. Clin Transl Med, 2021, 11(8): e492.
[11]	Rao Z, Zhu Y, Yang P, et al. Pyroptosis in inflammatory diseases and cancer[J]. Theranostics, 2022, 12(9): 4310-4329.
[12]	Swanson K V, Deng M, Ting J P. The NLRP3 inflammasome: Molecular activation and regulation to therapeutics[J]. Nat Rev Immunol, 2019, 19(8): 477-489. doi: 10.1038/s41577-019-0165-0
[13]	Fu J, Wu H. Structural mechanisms of NLRP3 inflammasome assembly and activation[J]. Annu Rev Immunol, 2023, 41: 301-316. doi: 10.1146/annurev-immunol-081022-021207
[14]	Zheng X, Chen W, Gong F, et al. The role and mechanism of pyroptosis and potential therapeutic targets in sepsis: A review[J]. Front Immunol, 2021, 12: 711939. doi: 10.3389/fimmu.2021.711939
[15]	Bauernfried S, Hornung V. Human NLRP1: From the shadows to center stage[J]. J Exp Med, 2022, 219(1): e20211405. doi: 10.1084/jem.20211405
[16]	Romberg N, Vogel T P, Canna S W. NLRC4 inflammasomopathies[J]. Curr Opin Allergy Clin Immunol, 2017, 17(6): 398-404. doi: 10.1097/ACI.0000000000000396
[17]	Wang B, Tian Y, Yin Q. AIM2 inflammasome assembly and signaling[J]. Adv Exp Med Biol, 2019, 1172: 143-155. doi: 10.1007/978-981-13-9367-9_7
[18]	Yu D, Zheng S, Sui L, et al. The role of AIM2 in inflammation and tumors[J]. Front Immunol, 2024, 15: 1466440. doi: 10.3389/fimmu.2024.1466440
[19]	Oh S, Lee J, Oh J, et al. Integrated NLRP3, AIM2, NLRC4, Pyrin inflammasome activation and assembly drive PANoptosis[J]. Cell Mol Immunol, 2023, 20(12): 1513-1526.
[20]	Liu Z, Wang C, Lin C. Pyroptosis as a double-edged sword: The pathogenic and therapeutic roles in inflammatory diseases and cancers[J]. Life Sci, 2023, 318: 121498. doi: 10.1016/j.lfs.2023.121498
[21]	Abu Khweek A, Amer A O. Pyroptotic and non-pyroptotic effector functions of caspase-11[J]. Immunol Rev, 2020, 297(1): e12910.
[22]	Rühl S, Broz P. Caspase-11 activates a canonical NLRP3 inflammasome by promoting K(+) efflux[J]. Eur J Immunol, 2015, 45(10): 2927-2936.
[23]	González P, Lozano P, Ros G, et al. Hyperglycemia and oxidative stress: An integral, updated and critical overview of their metabolic interconnections[J]. Int J Mol Sci, 2023, 24(11): 9352.
[24]	Russell-Guzmán J, Américo-Da Silva L, Cadagan C, et al. Activation of the ROS/TXNIP/NLRP3 pathway disrupts insulin-dependent glucose uptake in skeletal muscle of insulin-resistant obese mice[J]. Free Radic Biol Med, 2024, 222: 187-198. doi: 10.1016/j.freeradbiomed.2024.06.011
[25]	Ji K, Chen L, Wang X, et al. Integrating single-cell RNA sequencing with spatial transcriptomics reveals an immune landscape of human myometrium during labour[J]. Clin Transl Med, 2023, 13(4): e1234. doi: 10.1002/ctm2.1234
[26]	Liu P, Zhang Z, Li Y. Relevance of the pyroptosis-related inflammasome pathway in the pathogenesis of diabetic kidney disease[J]. Front Immunol, 2021, 12: 603416. doi: 10.3389/fimmu.2021.603416
[27]	Liu Y, Lei H, Zhang W, et al. Pyroptosis in renal inflammation and fibrosis: Current knowledge and clinical significance[J]. Cell Death Dis, 2023, 14: 472. doi: 10.1038/s41419-023-06005-6
[28]	Huang R, Fu P, Ma L. Kidney fibrosis: From mechanisms to therapeutic medicines[J]. Signal Transduct Target Ther, 2023, 8(1): 129. doi: 10.1038/s41392-023-01379-7
[29]	胡雪茹. 吴茱萸次碱对糖尿病肾病足细胞损伤的保护作用及相关机制研究[D]. 合肥: 安徽医科大学, 2022.
[30]	Feng L, Feng Y, Ren Q, et al. Mesangial cells in diabetic kidney disease: from mechanisms to therapeutic implications[J]. Int J Biol Sci, 2025, 21(11): 4762-4781. doi: 10.7150/ijbs.114907
[31]	Hu S, Hang X, Wei Y, et al. Crosstalk among podocytes, glomerular endothelial cells and mesangial cells in diabetic kidney disease: an updated review[J]. Cell Commun Signal, 2024, 22(1): 136.
[32]	Williams B M, Cliff C L, Lee K, et al. The role of the NLRP3 inflammasome in mediating glomerular and tubular injury in diabetic nephropathy[J]. Front Physiol, 2022, 13: 907504. doi: 10.3389/fphys.2022.907504
[33]	Thomas H Y, Ford Versypt A N. Pathophysiology of mesangial expansion in diabetic nephropathy: Mesangial structure, glomerular biomechanics, and biochemical signaling and regulation[J]. J Biol Eng, 2022, 16(1): 19.
[34]	Ostendorf T, Boor P, van Roeyen C R C, et al. Platelet-derived growth factors (PDGFs) in glomerular and tubulointerstitial fibrosis[J]. Kidney Int Suppl, 2014, 4(1): 65-69.
[35]	Melchinger I, Guo K, Li X, et al. VCAM-1 mediates proximal tubule-immune cell cross talk in failed tubule recovery during AKI-to-CKD transition[J]. Am J Physiol Renal Physiol, 2024, 327(4): F610-F622. doi: 10.1152/ajprenal.00076.2024
[36]	Thomas J M, Ling Y H, Huuskes B, et al. IL-18 (interleukin-18) produced by renal tubular epithelial cells promotes renal inflammation and injury during deoxycorticosterone/salt-induced hypertension in mice[J]. Hypertension, 2021, 78(5): 1296-1309. doi: 10.1161/HYPERTENSIONAHA.120.16437
[37]	Meng X M, Nikolic-Paterson D J, Lan H Y. TGF-β: The master regulator of fibrosis[J]. Nat Rev Nephrol, 2016, 12(6): 325-338. doi: 10.1038/nrneph.2016.48
[38]	Yu X Y, Sun Q, Zhang Y M, et al. TGF-β/smad signaling pathway in tubulointerstitial fibrosis[J]. Front Pharmacol, 2022, 13: 860588. doi: 10.3389/fphar.2022.860588
[39]	Wang W, Wang X, Chun J, et al. Inflammasome-independent NLRP3 augments TGF-β signaling in kidney epithelium[J]. J Immunol, 2013, 190(3): 1239-1249. doi: 10.4049/jimmunol.1201959
[40]	Liu Y, Lei H, Zhang W, et al. Pyroptosis in renal inflammation and fibrosis: Current knowledge and clinical significance[J]. Cell Death Dis, 2023, 14(7): 472. doi: 10.1038/s41419-023-06005-6
[41]	Coll R C, Hill J R, Day C J, et al. MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition[J]. Nat Chem Biol, 2019, 15(6): 556-559. doi: 10.1038/s41589-019-0277-7
[42]	Jiang H, He H, Chen Y, et al. Identification of a selective and direct NLRP3 inhibitor to treat inflammatory disorders[J]. J Exp Med, 2017, 214(11): 3219-3238. doi: 10.1084/jem.20171419
[43]	Burdette B E, Esparza A N, Zhu H, et al. Gasdermin D in pyroptosis[J]. Acta Pharm Sin B, 2021, 11(9): 2768-2782. doi: 10.1016/j.apsb.2021.02.006
[44]	Jin Y, Liu Y, Xu L, et al. Novel role for caspase 1 inhibitor VX765 in suppressing NLRP3 inflammasome assembly and atherosclerosis via promoting mitophagy and efferocytosis[J]. Cell Death Dis, 2022, 13(5): 512. doi: 10.1038/s41419-022-04966-8
[45]	Liu Z, Wang C, Rathkey J K, et al. Structures of the gasdermin D C-terminal domains reveal mechanisms of autoinhibition[J]. Structure, 2018, 26(5): 778-784. doi: 10.1016/j.str.2018.03.002
[46]	Dai Z, Liu W C, Chen X Y, et al. Gasdermin D-mediated pyroptosis: Mechanisms, diseases, and inhibitors[J]. Front Immunol, 2023, 14: 1178662.
[47]	Hu J J, Liu X, Xia S, et al. FDA-approved disulfiram inhibits pyroptosis by blocking gasdermin D pore formation[J]. Nat Immunol, 2020, 21(7): 736-745. doi: 10.1038/s41590-020-0669-6
[48]	Zahid A, Li B, Kombe A J K, et al. Pharmacological inhibitors of the NLRP3 inflammasome[J]. Front Immunol, 2019, 10: 2538. doi: 10.3389/fimmu.2019.02538
[49]	Suganya N, Dornadula S, Chatterjee S, et al. Quercetin improves endothelial function in diabetic rats through inhibition of endoplasmic reticulum stress-mediated oxidative stress[J]. Eur J Pharmacol, 2018, 819: 80-88. doi: 10.1016/j.ejphar.2017.11.034
[50]	Choe J Y, Kim S K. Quercetin and ascorbic acid suppress fructose-induced NLRP3 inflammasome activation by blocking intracellular shuttling of TXNIP in human macrophage cell lines[J]. Inflammation, 2017, 40(3): 980-994. doi: 10.1007/s10753-017-0542-4

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