Abstract
Pyroptosis is one special type of lytic programmed cell death, featured in cell swelling, rupture, secretion of cell contents and remarkable proinflammation effect. In the process of pyroptosis, danger signalling and cellular events are detected by inflammasome, activating caspases and cleaving Gasdermin D (GSDMD), along with the secretion of IL-18 and IL-1β. Pyroptosis can be divided into canonical pathway and non-canonical pathway, and NLRP3 inflammasome is the most important initiator. Diabetic kidney disease (DKD) is one of the most serious microvascular complications in diabetes. Current evidence reported the stimulatory role of hyperglycaemia-induced cellular stress in renal cell pyroptosis, and different signalling pathways have been shown to regulate pyroptosis initiation. Additionally, the inflammation and cellular injury caused by pyroptosis are tightly implicated in DKD progression, aggravating renal fibrosis, glomerular sclerosis and tubular injury. Some registered hypoglycaemia agents exert suppressive activity in pyroptosis regulation pathway. Latest studies also reported some potential approaches to target the pyroptosis pathway, which effectively inhibits renal cell pyroptosis and alleviates DKD in in vivo or in vitro models. Therefore, comprehensively compiling the information associated with pyroptosis regulation in DKD is the main aim of this review, and we try to provide new insights for researchers to dig out more potential therapies of DKD.
Highlights
According to the International Diabetes Federation Diabetes Atlas, 9th Edition, nearly one billion people are going to get diabetes around the world by 2020, and the data is expected to reach 25% higher by 2030, and 51% higher by 2045 [1]
Some of current studies have proved that hyperglycaemia, fatty acids and other damage associated molecules can be identified by some specific pattern recognition receptors (PRRs) in cells, and induce the occurrence of pyroptosis [2], which leads to kidney damage and function decline
Through the preceding foreshadowing, we summarize some present therapeutic avenues of Diabetic kidney disease (DKD) through the mechanism of pyroptosis regulation
Summary
According to the International Diabetes Federation Diabetes Atlas, 9th Edition, nearly one billion people are going to get diabetes around the world by 2020, and the data is expected to reach 25% higher by 2030, and 51% higher by 2045 [1]. Mediated by a variety of inflammatory factors, DKD is a metabolic disease with complex physiological and pathological mechanisms Various factors such as hyperglycaemia, lipid metabolism disorder, oxidative stress, and advanced glycosylation end products (AGEs) run through the whole progression of DKD. Some risk factors of DKD, including high glucose (HG), oxidative stress, abnormal lipid metabolism and AGEs, are strongly related with pyroptosis in the occurrence of DKD in present studies. We estimate the latest studies emerging in the roles of pyroptosis regulation of DKD in the current review, starting from the biology of pyroptosis to obtain an overview of the main mechanism, and going deep into the pyroptosis regulation in cell stress and NLRP3 inflammasome activation signalling pathways with DKD to lucubrate the association. We try to provide new insights for researchers to extract more potential therapies of DKD
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