The Role Of Macrophage Migration Inhibitory Factor In The Pathological Mechanisms Of Lupus Nephritis

Objective This study aimed to screen miRs that can regulate the expression of MIF,and investigate the contribution of MIF to lupus nephritis involved in the abnormal activation of Hippo pathway.Methods Real-time PCR was used to detect the MIF expression in PBMC and kidneysfrom SLE patients and controls,and enzyme-linked immuno sorbent assay(ELISA)was used to detect MIF expression in the plasma from SLE patients.Luciferase reporter assays was used to screen miRs that can regulate the MIF expression,and furthermore,those miRs were verified by ELISA and western blot.Cell proliferation and inflammation cytokines were detected afterover-expression miR-654.After over-expression miR-654 in C57/B6 mouse,murine lupus were induces by pristane intraperitoneally,the sera autoantibodies and cytokines were derected by ELISA,histopathology of kidney were examined by immunofluorescence and periodic acid-schiff stain(PAS).RT-PCR were used to detect the m RNA expression level of individual genes relevant to Hippo pathway in HEK293 after MIF were knock out.Inflammation cytokines were examined by ELISA after overexpression CYR61 or knockout CYR61.Sera CYR61 from miR-654 group and NC group were detected by ELISA.RT-PCR were used to detect the expression level of MIF m RNA and CYR61 m RNA in the PBMC from SLE patients and control.Statistical software were used to analyze the differentiation between groups and correlation between variates.Result MIF expression is higher in PBMC?plasma and kidneys from SLE patients than in controls.miR-654 can significantly inhibit MIF expression by targeting the 3' UTR of MIF,it can inhibit cell proliferation and the expression of inflammation cytokines.miR-654 have a protective role in the pathogenesis of lupus nephritis in pristane-induced murine lupus model.MIF can promote cell proliferation and inflammation cytokines expression by upregulating CYR61.Sera CYR61 expression from miR-654 group is higher than in NC groups.The expression levels of CYR61 and MIF were higher in PBMC from SLE patients than in controls.Cyr61 expression is positively related with SLEDAI,and there was a positive relationship between the CYR61 m RNA expression and MIF m RNA expression.Conclusion miR-654 have a protective role in the pathogenesis of lupus nephritis by targeting MIF;MIF is involed in the pathogenesis of lupus nephritis by prompting the expression of CYR61,and CYR61 maybe a new treat target in lupus nephritis.