细胞焦亡主要表现为细胞肿胀,形成缺乏离子选择性的孔隙,引起"焦亡小体"样泡状突起,最终造成质膜裂解,释放炎症因子.细胞焦亡主要由炎性半胱天冬酶(cysteinylaspartate specific proteinase,caspase)介导,包括由caspase-1介导的经典焦亡途径和caspase-4/5/11介导的非经典焦亡途径,通过触发下游的消皮素D(gasdermin,GSDMD),引起细胞膜穿孔,从而释放细胞内容物和大量的炎性细胞因子,诱发细胞焦亡.近年来,越来越多的证据表明细胞焦亡参与糖尿病肾脏疾病(dia-betic kidney disease,DKD)疾病进展,可能成为DKD的潜在治疗靶点.本文将对细胞焦亡在DKD疾病进展的相关研究进行综述,总结现阶段肾脏固有细胞焦亡在DKD发病机制中的作用及靶向细胞焦亡的相关药物研究,以期为DKD疾病机制研究与治疗策略的更新提供新的思路.
Mechanism of action and research progress of pyroptosis in diabetic kidney disease
Cell pyroptosis is characterized by cellular swelling and the formation of ion non-selective pores,leading to the emergence of"pyroptotic body-like"vesicular protrusions,ultimately resulting in plasma membrane lysis and the release of inflammatory factors.Cell pyroptosis is mainly mediated by inflammatory cysteinyl aspartate specific proteinase(caspase),including the classical pyroptotic pathway mediated by caspase-1 and the non-classical pyroptotic pathway mediated by caspase-4/5/11.This process triggers down-stream gasdermin to cause cell membrane perforation,thus leading to the release of cellular contents and numbers of inflammatory cyto-kines and inducing cell pyroptosis.In recent years,increasing evidence suggests that cell pyroptosis is involved in the progression of diabetic kidney disease(DKD)and may serve as a potential therapeutic target for DKD.This article provides a review of the relevant re-search on cell pyroptosis in the progression of DKD and summarizes the current understanding of the role of intrinsic renal cell pyropto-sis in the pathogenesis of DKD and drug studies targeting cell pyroptosis,aiming to offer new insights for updating research on the mechanisms and treatment strategies of DKD.
diabetic kidney diseasepyroptosisNOD-like receptor thermal protein domain associated protein 3
万方数据
维普
