Study On Inflammatory Response Of IgA Nephropathy Mediated By MiRNA-29 Through C3AR1

Objective IgA nephropathy((IgAN))is the most common glomerular disease.Cell proliferation,fibrosis,apoptosis,persistent,inflammation and extracellular matr ix proliferation are all involved in the pathogenesis of IgAN.However,at present,th e molecular mechanism of the pathogenesis of IgAN has not been fully elucidated.In this study,an integrated bioinformatics analysis was used to further explore new potential gene targets of IgAN in order to further understand the mechanism of infl ammatory response in the pathogenesis of IgA nephropathy.Method Based on the comprehensive gene expression database(GEO database),the selected microarray wa s downloaded and differentially expressed genes were screened by online tool GEO 2R,then the target genes were analyzed by GO and KEGG using DAVID database,the protein interactions of differentially expressed genes were analyzed by STRIN G,and the key genes C3AR1 were screened by Cytoscape software.The relative m RNA expression of C3AR1 and miRNA-29 and the levels of cytokines IL-1β,IL-6,MCP-1,TNF-α and TGF-β mRNA in renal biopsy tissues of 30 patients with IgA and 15 patients undergoing nephrectomy for renal tumor were detected by real-time fluorescence quantification(qRT-PCR).Results The main results were as follows:(1)A total of 289 differentially expressed genes were screened by GEO database,a nd 25 HUB genes were found by Cytoscape.(2)The genes related to functional en richment and inflammation were PTPRC,IL10RA,ITGAM,HCK,CCR1,CSF1R,C3AR1,TLR2,C1QA,CCR5,CCL4,NCF and CD300A.(3)Compared with the c ontrol group,the expression of miRNA-29 mRNA decreased and C3AR1 mRNA in creased in IgAN group,and there was a significant negative correlation between mi RNA-29 and C3AR1.(4)The expression of IL-1β,IL-6,TNF-α and TGF-β mRNA increased(P<0.001),the expression level of chemokine MCP-1 mRNA increased(P<0.001);(5)C3AR1 was positively correlated with IL-1β,IL-6,MCP-1,TNF-α and TGF-β,while miRNA-29 was negatively correlated with IL-1β,IL-6,MCP-1,TNF-α and TGF-β.Conclusions MiRNA-29 may be involved in the activation of infla mmatory response in IgA nephropathy by regulating C3AR1.