Study On Corilagin Counteracting IL-13R?1 Signaling Pathway In M2 Macrophages To Mitigate Schistosomiasis Hepatic Fibrosis

Objectives: IL-13 induces M2 polarization in macrophages through IL-13/STAT6 signaling pathway via binding to IL-13R?1,and it plays crucial roles in fibrosis via promoting the expression of pro-fibrotic molecules,especially in schistosomiasis-induced hepatic fibrosis,renal fibrosis and pulmonary fibrosis.This study aims to investigate the inhibitory effect and mechanism of action of corilagin on fibrosis via IL-13/STAT6 signaling pathway in M2 macrophages in vitro and in vivo.Methods: Murine macrophage cell line Ana-1 was utilized as cell model,and C57BL/6 mice infected with Schistosoma japonicum cercaria were utilized as animal model.IL-13/STAT6 signaling pathway was activated by IL-13 in vitro,and the adult schistosomes was effectively killed by praziquantel before corilagin administration in vivo.The mRNA and protein expression of IL-13R?1,PPAR?,KLF4,SOCS1,STAT6,p-STAT6,and TGF-? was measured with corilagin treatment after IL-13 stimulation by real-time qPCR,western blot assay or ELISA.Histological analysis of liver tissue was assessed for the degree of hepatic fibrosis and M2 macrophage distribution.Results: The results revealed that corilagin significantly reduced the expression of PPAR?,KLF4,SOCS1,p-STAT6,and TGF-? compared with model group(p < 0.01 or p < 0.05),which indicated a strong inhibitory effect of corilagin on IL-13/STAT6 signaling pathway.As well,the inhibitory effect of corilagin showed significant dose-dependence(p < 0.05).Furthermore,the anti-fibrogenic effect persisted even when IL-13R?1 was up-or down-regulated in Ana-1 cells.The area of fibrosis and distribution of M2 macrophages in mouse liver tissue were reduced significantly and dose-dependently with corilagin treatment compared to model group or praziquantel administration(p < 0.01 or p < 0.05),indicating that corilagin suppressed IL-13/STAT6 signaling pathway and M2 macrophage polarization effectively in vitro and in vivo.Conclusion: Corilagin can suppress fibrosis via inhibition of M2 macrophage polarization in IL-13/STAT6 signaling pathway.