Exosomal miR-30a-5p targets NLRP3 to suppress podocyte pyroptosis in diabetic nephropathy

Background:Mesenchymal stem cell(MSC)-derived exosomes are closely related to pyroptosis in diabetic nephropathy(DN).This study aimed to explore the protective effect of exosomal miR-30a-5p on podocyte pyroptosis in DN.Methods:Streptozotocin was used to establish the mouse model of DN.Human bone marrow MSC-derived exosomes were extracted and identified via transmission electron microscopy,nanoparticle tracking analysis,and western blotting.MiR-30a-5p mimics and non-control(NC)mimics were transfected into MSCs and podocytes,and exosomes were isolated from the MSCs.High glucose(HG)-induced podocyte model was established to determine the effect of exosomal miR-30a-5p on pyroptosis and inflammation in vitro.Results:MiR-30a-5p was expressed at low levels in DN models,while NLR family pyrin domain containing 3(NLRP3),caspase-1,gasdermin-N(GSDMD-N),and pro-inflammatory factors(tumor necrosis factor-alpha,interleukin(IL)-1beta,and IL-18)were augmented.In vitro,miR-30a-5p expression in the HG-damaged podocytes was down-regulated,while NLRP3 was up-regulated.Interestingly,miR-30a-5p overexpression diminished HG-induced podocyte injury,as proven by increased activity and decreased pyroptosis of podocytes.Concurrently,the up-regulation of miR-30a-5p could inhibit the expression of pro-inflammatory factors,caspase-1,GSDMD-N,and NLRP3 in HG-induced podocytes.MSC-derived exosomal miR-30a-5p treatment of HG-damaged cells has similar effects to miR-30a-5p mimics treatment.Overexpression of NLRP3 reversed the effect of miR-30a-5p mimics on HG-induced podocytes.Conclusion:This research confirmed that exosomal miR-30a-5p regulates pyroptosis via mediating NLRP3 in DN.