A study about the role of Wip1 in renal fibrosis by modulating macrophage phenotype

objective To investigate the effect of wild type p53-induced phosphatase 1 (Wip1) on regulation the phenotype of macrophages and to participate in renal fibrosis. Method: RAW264.7 macrophages were stimulated by lipopolysaccharide (LPS) and IFN-γ for 24h into M1 macrophages with high expression of iNOS and TNF-α. RAW264.7 macrophages were stimulated by interleukin 4(IL-4) for 24 h to induce M2 macrophages with high expression of Arg-1 and CD206. In the meantime, RAW264.7 macrophages were transduced with Wip1 lentivirus by overexpressing it, and transduced with Wip1 RNAi by reducing the Wip1 expression. Furthermore, after coculture the transformed macrophages and mice primary renal tubular epithelial cells, and the expression levels of E-Cadhrin, Vimentin and α-SMA were measured by RT-PCR. Result: it was found that macrophages with Wip1 overexpression had no statistical changes on the expression of iNOS and showed the decreased expression of TNF-α; macrophages with Wip1 siRNA showed the increased expression of iNOS and TNF-α compared to control group. In the meantime, macrophages with Wip1 overexpression had increased expression of Arg-1 and CD206; macrophages with Wip1 siRNA showed decreased expression of Arg-1 and CD206 compared to control group. Macrophage RAW264.7could be transformed into the M2 macrophage after transducing with Wip1 lentivirus by overexpressing it, and the RAW264.7 macrophages could transform into the M1 macrophages by reducing the Wip1 expression via the Wip1 RNAi. Furthermore, after coculture the M2 macrophage and mice primary renal tubular epithelial cells, there was a decreased E-Cadherin expression, increased Vimentin, and α-SMA on the mRNA levels. Conclusion: Wip1 in macrophages may participate in the pathophysiological process in the renal tubulointerstitial fibrosis by transforming them into the M2 macrophage phenotype.