Pyroptosis is a recently identified type of lytic programmed cell death, in which pores form in the plasma membrane, and cells swell, rupture, and then release their contents, including inflammatory cytokines. Molecular studies indicated that pyroptosis may occur via a gasdermin D (GSDMD) and caspase-1 (Casp1) -dependent classical pathway, a GSDMD and Casp11/4/5-dependent non-classical pathway, or a gasdermin E (GSDME) and Casp3-dependent pathway. Studies of animal models and humans indicated that pyroptosis can exacerbate several complications of diabetes, including diabetic nephropathy (DN), a serious microvascular complication of diabetes. Many studies investigated the mechanism mediating the renoprotective effect of GSDMD regulation in the kidneys of patients and animal models with diabetes. As a newly discovered regulatory mechanism, GSDME and Casp3-dependent pyroptotic pathway in the progression of DN has also attracted people’s attention. Z-DEVD-FMK, an inhibitor of Casp3, ameliorates albuminuria, improves renal function, and reduces tubulointerstitial fibrosis in diabetic mice, and these effects are associated with the inhibition of GSDME. Studies of HK-2 cells indicated that the molecular and histological features of secondary necrosis were present following glucose stimulation due to GSDME cleavage, such as cell swelling, and release of cellular contents. Therefore, therapies targeting Casp3/GSDME-dependent pyroptosis have potential for treatment of DN. A novel nephroprotective strategy that employs GSDME-derived peptides which are directed against Casp3-induced cell death may be a key breakthrough. This mini-review describes the discovery and history of research in this pyroptosis pathway and reviews the function of proteins in the gasdermin family, with a focus on the role of GSDME-mediated pyroptosis in DN. Many studies have investigated the impact of GSDME-mediated pyroptosis in kidney diseases, and these studies used multiple interventions, in vitro models, and in vivo models. We expect that further research on the function of GDSME in DN may provide valuable insights that may help to improve treatments for this disease.

Pyroptosis 是最近发现的一种裂解性程序性细胞死亡类型，其中质膜中形成孔，细胞膨胀、破裂，然后释放其内容物，包括炎性细胞因子。分子研究表明可能发生细胞焦亡通过gasdermin D (GSDMD) 和 caspase-1 (Casp1) 依赖的经典通路，GSDMD 和 Casp11/4/5 依赖的非经典通路，或 gasdermin E (GSDME) 和 Casp3 依赖的通路。对动物模型和人类的研究表明，细胞焦亡会加剧糖尿病的多种并发症，包括糖尿病肾病 (DN)，这是一种严重的糖尿病微血管并发症。许多研究调查了调节 GSDMD 调节在糖尿病患者和动物模型肾脏中的肾脏保护作用的机制。作为一种新发现的调控机制，GSDME 和 Casp3 依赖的 DN 进展过程中的细胞焦亡通路也引起了人们的关注。Z-DEVD-FMK 是一种 Casp3 抑制剂，可改善白蛋白尿、改善肾功能并减少糖尿病小鼠的肾小管间质纤维化，这些作用与 GSDME 的抑制有关。HK-2 细胞的研究表明，由于 GSDME 裂解，葡萄糖刺激后出现继发性坏死的分子和组织学特征，例如细胞肿胀和细胞内容物的释放。因此，针对 Casp3/GSDME 依赖性细胞焦亡的疗法具有治疗 DN 的潜力。一种使用 GSDME 衍生肽针对 Casp3 诱导的细胞死亡的新型肾保护策略可能是一个关键的突破。这篇小型综述描述了这一细胞焦亡途径的发现和研究历史，并回顾了 gasdermin 家族中蛋白质的功能，重点是 GSDME 介导的焦亡在 DN 中的作用。许多研究调查了 GSDME 介导的细胞焦亡对肾脏疾病的影响，体外 模型，和 体内楷模。我们希望进一步研究 GDSME 在 DN 中的功能可能会提供有价值的见解，可能有助于改善对该疾病的治疗。