Cyclophosphamide can up-regulate miR-223 expression, promote M2 polarization of macrophage and reduce inflammation level in membranous nephropathy

This study aimed to investigate the role of the immune and inflammatory modulator miR-223 in the immunosuppressive and anti-inflammatory effects of cyclophosphamide (CTX) in membranous nephropathy (MN). To this end, we first developed an LPS-induced inflammatory cell line treated with CTX in which we modulated miR-223 levels using either an miR-223 mimic or inhibitor. The level of miR-223 in the LPS-induced inflammation model group was lower than that in the control group. The levels of inflammatory factors in the LPS + miR-223 mimic and CTX + miR-223i groups were lower than those in the LPS and miR-223i groups. The protein levels of macrophage M2 phenotype markers Arg1 and TGF-β1 and anti-inflammatory factors IL4 and IL13 in the LPS+miR-223 mimic group and CTX+miR-223i group were significantly higher than those in the LPS group and miR-223i group, and the ratio of Egr2+/CD38 + in the LPS + miR-223 mimic group and CTX + miR-223i group was also higher. The effect of CTX was confirmed in the MN model of BALB/c mice induced by c-BSA. In conclusion, CTX can upregulate the expression of miR-223, promote the polarization of M2 macrophages, and alleviate inflammatory response and renal injury in MN.