The roles of Toll-like receptor 4 in the pathogenesis of pathogen-associated biliary fibrosis caused by Clonorchis sinensis

作者：Chao Yan, Bo Li, Fang Fan, Ying Du, Rui Ma, Xiao-Dan Cheng, Xiangyang Li, Bo Zhang, Qian Yu, Yugang Wang, Renxian Tang, Kuiyang Zheng · 发表于：Scientific Reports · 年份：2017 · DOI：10.1038/s41598-017-04018-8 · 被引用次数：28 · 研究领域：Liver physiology and pathology、Gallbladder and Bile Duct Disorders、Pediatric Hepatobiliary Diseases and Treatments

Abstract Pathogen-associated biliary fibrosis (PABF) is a type of liver fibrosis characterized by injuries of cholangiocytes and extra cellular matrix (ECM) deposition around bile ducts caused by various bacteria, fungi, virus and parasites. Recent studies show that TLR4 plays an important role in several other types of liver fibrosis, but the mechanism of TLR4 in PABF is yet really unclear. In the present study, a PABF mouse model was established by a trematode infection- Clonorchis sinensis which dwells in the bile ducts and causes severe biliary fibrosis of mice. The results showed that the levels of collagen depositions, α-SMA and hydroxyproline (Hyp) contents in TLR4 mut mice infected by C . sinensis were significantly lower than in those of TLR4 wild ones. Furthermore, we found that the activation of TGF-β signaling was impaired in the TLR4 mut mice, compared with wild mice when they were challenged to the same dose of C . sinensis metacercariae. Moreover, the mice with TLR4 mutation showed a decreased activation of hepatic stellate cells indicated by the expression of α-SMA, when compared with TLR4 wild mice. These data demonstrate that TLR4 contributes to PABF caused by C . sinensis and TLR4 signaling may be a potential medical target for treatment of PABF.