#2006 CircMTND5 participated in tubulointerstitial fibrosis progression of lupus nephritis by binding with A1CF

Abstract

Abstract Background and Aims lupus nephritis (LN) is the most common and severe complication of systemic lupus erythematosus (SLE). CircRNA MTND5 participated in the pathogenesis of LN by sponging miR6812. However, it remains unclear what RNA binding role of circMTND5 play in LN. We aim to investigate whether circMTND5 can interact with RBP in the development and progression in LN, and to clarify the corresponding mechanisms. Method A1CF, a RNA binding protein, E-cadherin, α-SMA, TGF-β, and Fibronectin were analyzed by immunohistochemistry on paraffin-embedded section of LN patients and NC kidney tissues. The above parameters and circMTND5 were also examined in Fcgr2b-/- spontaneous LN mice kidneys by Western blotting and qPCR. In human kidney (HK) -2 cells, the binding of circMTND5 to A1CF protein was examined by RNA immunoprecipitation (RIP) assay. After knockdown in HK-2 cells and overexpression in hTGF-β stimulated HK-2 cells, we examined the all above indices. Results the expression of A1CF was down-regulated in the kidneys of LN patients and was localized in tubular epithelial cells. E-cadherin was down-regulated while α-SMA was up-regulated. The expression of circMTND5 was down-regulated in kidneys of Fcgr2b-/- spontaneous LN mice. In HK-2 cells, the binding of circMTND5 to A1CF was confirmed by RIP. A1CF and E-cadherin were down-regulated, while α-SMA, TGF-β and FN were up-regulated in HK-2 cells with knockdown of circMTND5. The overexpression of circMTND5 reverted the changes of the those above parametered induced by hTGF-β in both mRNA and proteins levels. Conclusion The expression level of circMTND5 in renal tissue of LN mice was downregulated. CircMTND5 might play an important role in tubulointerstitial fibrosis of lupus nephritis by binding with A1CF protein.