Interferon-α1b ameliorates EMT and fibrosis of renal tubular epithelial cells in IgA nephropathy by miRNA-141 suppressing ZEB1/SIP1 signaling pathway
Objective To investigate the effect of interferon-α1b on improving EMT and fibrosis of renal tubular epithelial cells in IgA nephropathy by inhibiting ZEB1/SIP1 signaling pathway through miR141.Methods MDCK cell model was used to verify the effects of interferon-α1b on miR-141 expression and ZEB1/SIP1 signaling pathway.Rats model of IgA nephropathy was established,and randomly divided into control group,model group,interferon-α1b(15,30 μg)group,and prednisone group,with 8 rats in each group,for continuous treatment for 8 weeks.Renal function,levels of inflammatory factors,IgA deposition and renal pathological changes were monitored.The expression levels of miR-141,ZEB1,SIP1 and E-cadherin were analyzed.Results In vitro experiments showed that interferon-α1b could significantly up-regulate the expression of miR-141 in MDCK cells,and reduce the relative expression levels of ZEB1 and SIP1 proteins(P<0.05).In the rat model of IgA nephropathy,compared the model group,the renal function of the rats in the interferon-α1b group was significantly improved,the secretion levels of inflammatory TNF-α and IL-6 were significantly decreased,the deposition of IgA was reduced,and the kidney injury was alleviated(P<0.05).Interferon-α1b can induce significantly up-regulated miR-141 in rat kidney,inhibit the relative expression of ZEB1 and SIP1 proteins,up-regulate the relative expression of E-cadherin protein,and inhibit EMT and fibrosis in epithelial cells(P<0.05).Conclusion Interferon-α1b effectively improves IgA nephropathy by upregulating the expression of miR-141 in the kidney,inhibiting the expression of transcription factors ZEB1 and SIP1,reducing the inhibition of E-cadherin,and ultimately inhibiting renal tubular epithelial cell EMT and fibrosis.
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