Abstract
Pyroptosis is a recently identified mechanism of programmed cell death related to Caspase-1 that triggers a series of inflammatory reactions by releasing several proinflammatory factors such as IL-1β and IL-18. The process is characterised by the rupture of cell membranes and the release of cell contents through the mediation of gasdermin (GSDM) proteins. GSDMD is an important member of the GSDM family and plays a critical role in the two pathways of pyroptosis. Diabetic nephropathy (DN) is a microvascular complication of diabetes and a major cause of end-stage renal disease. Recently, it was revealed that GSDMD-mediated pyroptosis plays an important role in the occurrence and development of DN. In this review, we focus on two types of kidney cells, tubular epithelial cells and renal podocytes, to illustrate the mechanism of pyroptosis in DN and provide new ideas for the prevention, early diagnosis and molecular therapy of DN.
Highlights
Diabetic nephropathy (DN), one of the main complications of diabetes mellitus (DM), is the main cause of end-stage renal disease (ESRD) (Ref. 1).So far, it has been found that cell death exists in the process of DN, such as apoptosis, necrosis, autophagy, pyroptosis, ferroptosis and so on (Refs [2,3,4,5,6])
Zhu et al (Ref. 94) found that the expression of KCNQ1OT1 is increased in High glucose (HG)-induced HK-2 cells and in the plasma of DN patients. They confirmed that KCNQ1OT1 directly targets miR-506-3p using a luciferase assay. They showed that the expression of miR-506-3p is downregulated in HG-treated HK-2 cells and in the plasma of patients with DN, and that KCNQ1OT1 interference could reduce the levels of caspase-1, NLRP3 and GSDMD-NT by upregulating the expression of miR-506-3p, thereby alleviating inflammation, oxidative stress (OS) and the pyroptosis of HG-induced HK-2 cells
Under the action of different external stimuli, the cell membrane is punctured via the GSDMD protein through different channels, which leads to cell rupture, necrosis and the flowing out of cell contents
Summary
Diabetic nephropathy (DN), one of the main complications of diabetes mellitus (DM), is the main cause of end-stage renal disease (ESRD) (Ref. 1).So far, it has been found that cell death exists in the process of DN, such as apoptosis, necrosis, autophagy, pyroptosis, ferroptosis and so on (Refs [2,3,4,5,6]). A recent study found that GSDMB can induce pyroptosis-like characteristics, but the mechanism whereby GSDMB activity leads to pyroptosis and participates in the regulation of inflammation needs to be further explored (Ref. 43). On the other hand, activated caspase-1 can directly cleave GSDMD, causing the release of GSDMD-NT and leading to cell membrane pore formation and pyroptosis.
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