Corilagin Counteracts IL-13Rα1 Signaling Pathway in Macrophages to Mitigate Schistosome Egg-Induced Hepatic Fibrosis

Frontiers in Cellular and Infection Microbiology

Zhao, Lei¹  Chen, Yun-Fei²  Wang, Yu-Jie²  Li, Yi-Qing²  Dang, Yi-Ping²  Shang, Zhen-Zhong³  Li, Quan-Qiang⁴  Wang, Yao⁵  Zhang, Juan⁵  Luo, Lei⁵  Ma, Qian⁶ 

[1] Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China;Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China;School of Basic Medical Sciences, Guangxi University of Chinese Medicine, China;School of Clinical Medicine, Guangxi University of Chinese Medicine, China;School of Clinical Medicine, Hubei University of Chinese Medicine, China;School of Life Science, Hubei University, China

关键词: Corilagin;    liver fibrosis;    schistosome egg;    IL-13Rα1;    M2 macrophage;   

DOI  :  10.3389/fcimb.2017.00443

学科分类：生物科学（综合）

来源: Frontiers

【 摘 要 】

The IL-13Rα1 signalling pathway and M2 macrophages play crucial roles in schistosome egg-induced hepatic fibrosis via the expression of pro-fibrotic molecules. This study aims to investigate the inhibitory effect and mechanism of action of corilagin on schistosome egg-induced hepatic fibrosis via the IL-13Rα1 signalling pathway in M2 macrophages in vitro and in vivo. The mRNA and protein expression of IL-13Rα1, PPARγ, KLF4, SOCS1, STAT6, p-STAT6 and TGF-β was measured in vitro with corilagin treatment after IL-13 stimulation and in vivo corilagin treatment after effectively killing the adult schistosomes in schistosome-infected mice. Histological analysis of liver tissue was assessed for the degree of hepatic fibrosis. The results revealed that corilagin significantly reduced the expression of PPARγ, KLF4, SOCS1, p-STAT6 and TGF-β compared with model group and praziquantel administration (p<0.01 or p<0.05) in vivo and in vitro, which indicated a strong anti-fibrogenic effect of corilagin. As well, the inhibitory effect of corilagin showed a significant dose-dependence (p<0.05). 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 supressed IL-13Rα1 signalling pathway and M2 macrophage polarization effectively in vivo. Furthermore, the anti-fibrogenic effect persisted even when IL-13Rα1 was up- or down-regulated in vitro. In conclusion, corilagin can suppress schistosome egg-induced hepatic fibrosis via inhibition of M2 macrophage polarization in the IL-13Rα1 signalling pathway.

【 授权许可】

CC BY