Mechanism of gasdermin D protein-mediated pyroptosis in alleviating kidney injury of mice induced by hyperuricemia
Objective:To investigate the role and mechanism of pyroptosis execution gasdermin D protein(GSDMD)in alleviating the kidney injury of mice induced by hyperuricemia(HUA).Methods:C57BL/6J WT and GSDMD knockout mice were selected as experimental animals,and divided into groups of WT-Norm-diet,WT-HUA,KO-Norm-diet and KO-HUA.Potassium oxonate(250 mg/(kg·day))and adenine(50 mg/(kg·day))were administered by gavage for 28 days to establish the HUA model.Blood was collected to measure the uric acid and creatinine levels.Hematoxylin and eosin(HE)staining was used to observe tissue morphological changes.The expressions of GSDMD and GSDMD-N in renal cortex were measured by Western blot.KIM-1 and NAGL mRNA levels were determined by RT-PCR.Results:Compared with the WT-Norm-diet group,the serum levels of uric acid were higher in the WT-HUA group(P＜0.01).Western blot results showed that the GSDMD and GSDMD-N protein level were significantly increased in the WT-HUA group compared with the WT-Norm-diet group(P＜0.01).RT-PCR revealed that KIM-1 mRNA level was significantly up-regulated in the WT-HUA group(P＜0.01).Compared with the WT-HUA group,the serum levels of uric acid,creatinine and NAGL mRNA expression were significantly lower in KO-HUA group(P＜0.05).The HE exhibited tubular necrosis,tubular extension and inflammatory cell infiltration in the kidney tissues in mice from the WT-HUA group,yet reduced tubular damage in the KO-HUA group.Conclusion:GSDMD knockout can effectively mitigate the kidney injury caused by hyperuricemia.
hyperuricemiakidney injurypyroptosisgasdermin D protein
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维普
