Abstract:

Ｏｂｊｅｃｔｉｖｅ：To explore the potential role and mechanism of microRNA497 in the glomerular mesangial cell pyroptosis induced by high glucose and insulin.
Ｍｅｔｈｏｄｏｌｏｇｙ：High glucose and insulin was used to treat human renal mesangial cells (HRMC). At various time points, cell pyroptosis was detected with flow cytometry, and realtime qPCR was used to detect miR497 levels in HRMC. Then, various concentrations of miR497 mimic were transfected to HRMC. The mRNA levels of key genes in pyroptotic pathway, including IL1β, TNFα and caspase1 were detected. Bioinformatics and Luciferase Reporter Gene assay were used to predict and verify the target of miR497 to nucleotidebinding oligomerization domain receptor P1 (NLRP1) inflammasome. The miR497 mimic and pcDNANLRP1 expression vector were transfected individually or cotransfected to HRMC. Western blotting was used to detect the levels of NLRP1 protein, and cell pyroptosis were detected.
Ｒｅｓｕｌｔｓ：HRMC treated with high glucose and insulin for more than 48h, HRMC pyroptosis was significantly increased, and the expression level of miR497 was decreased (P<005). After transfected with miR497 mimic, the pyroptosis of HRMC was significantly ameliorated, and the mRNA expression of IL1β, TNFα and caspase1 were downregulated (P<005). miR497 directly targeted at NLRP1 gene and suppressed NLRP1 protein expression. NLRP1 overexpression completely rescued the inhibition of cell pyroptosis caused by miR497.
Ｃｏｎｃｌｕｓｉｏｎ：The HRMC pyroptosis was suppressed miR497, and inflammation response was induced by high glucose and insulin.

Key words: pyroptosis, high glucose and insulin, microRNA-497, NLRP1 inflammasome, caspase1