CircMTND5 participates in tubulointerstitial injury in lupus nephritis by binding with A1CF protein.

BACKGROUND AND AIMS: Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus. CircRNA MTND5 (circMTND5) contributes to the pathogenesis of LN by sponging miR6812. However, it remains unclear what role RNA binding protein to circMTND5 might play. We investigated whether circMTND5 interacts with RNA binding proteins (RBP) in the progression of LN, and to clarify the mechanisms.

METHODS

A1CF (an RNA binding protein), E-cadherin, α-smooth muscle actin, TGF-β, and fibronectin were analyzed by immunostaining in paraffin-embedded section of kidney from patients with lupus and healthy controls. These proteins and circMTND5 were also examined in Fcgr2b-/- spontaneous LN mouse kidneys by Western blot and qPCR. In human kidney (HK)-2 cells, binding of circMTND5 to A1CF protein was examined by RNA immunoprecipitation (RIP). We examined the above indices after knockdown in HK-2 cells and over-expression in hTGF-β stimulated HK-2 cells,

RESULTS

A1CF expression was down-regulated in kidneys of LN patients and was localized to tubular epithelial cells. Expression of E-cadherin was down-regulated, while α-SMA expression was up-regulated. The expression of circMTND5 was down-regulated in kidneys of LN mice. In HK-2 cells, binding of circMTND5 to A1CF was confirmed by RIP. A1CF and E-cadherin were down-regulated, while α-SMA, TGF-β and fibronectin were up-regulated in HK-2 cells with knockdown of circMTND5. Over-expression of circMTND5 reversed the changes of the above parameters induced by hTGF-β at both mRNA and proteins levels.

CONCLUSIONS

circMTND5 may alleviated tubulointerstitial fibrosis in lupus nephritis by binding A1CF.