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鞣花酸通过抑制巨噬细胞中 IL-13Rα1 信号通路减轻血吸虫卵诱导的肝纤维化。

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

机构信息

Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

School of Clinical Medicine, Hubei University of Chinese Medicine, Wuhan, China.

出版信息

Front Cell Infect Microbiol. 2017 Oct 18;7:443. doi: 10.3389/fcimb.2017.00443. eCollection 2017.

DOI:10.3389/fcimb.2017.00443
PMID:29094025
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5651236/
Abstract

The IL-13Rα1 signaling 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 signaling pathway in M2 macrophages and . The mRNA and protein expression of IL-13Rα1, PPARγ, KLF4, SOCS1, STAT6, p-STAT6, and TGF-β was measured with corilagin treatment after IL-13 stimulation and 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 ( < 0.01 or < 0.05) and , which indicated a strong inhibitory effect of corilagin on IL-13Rα1 signaling pathway. As well, the inhibitory effect of corilagin showed a significant dose-dependence ( < 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 ( < 0.01 or < 0.05), indicating that corilagin suppressed IL-13Rα1 signaling pathway and M2 macrophage polarization effectively . Furthermore, the anti-fibrogenic effect persisted even when IL-13Rα1 was up- or down-regulated . In conclusion, corilagin can suppress schistosome egg-induced hepatic fibrosis via inhibition of M2 macrophage polarization in the IL-13Rα1 signaling pathway.

摘要

IL-13Rα1 信号通路和 M2 巨噬细胞通过表达促纤维化分子在血吸虫卵诱导的肝纤维化中起关键作用。本研究旨在探讨柯里拉京通过 M2 巨噬细胞中的 IL-13Rα1 信号通路对血吸虫卵诱导的肝纤维化的抑制作用及其作用机制。用柯里拉京处理后,用 IL-13 刺激并在感染血吸虫的小鼠中有效杀死成虫后,测量 IL-13Rα1、PPARγ、KLF4、SOCS1、STAT6、p-STAT6 和 TGF-β 的 mRNA 和蛋白表达。对肝组织进行组织学分析,评估肝纤维化程度。结果表明,与模型组和吡喹酮给药组相比,柯里拉京显著降低了 PPARγ、KLF4、SOCS1、p-STAT6 和 TGF-β 的表达(<0.01 或 <0.05),表明柯里拉京对 IL-13Rα1 信号通路有很强的抑制作用。此外,柯里拉京的抑制作用呈明显的剂量依赖性(<0.05)。与模型组或吡喹酮给药组相比,柯里拉京处理显著减少了纤维化面积和 M2 巨噬细胞在小鼠肝组织中的分布,且呈剂量依赖性(<0.01 或 <0.05),表明柯里拉京有效抑制了 IL-13Rα1 信号通路和 M2 巨噬细胞极化。此外,即使上调或下调 IL-13Rα1,抗纤维化作用仍然持续。综上所述,柯里拉京可通过抑制 IL-13Rα1 信号通路中的 M2 巨噬细胞极化来抑制血吸虫卵诱导的肝纤维化。

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