title: Toll like receptor 2 knock-out attenuates carbon tetrachloride (CCl4)-induced liver fibrosis by downregulating MAPK and NF-κB signaling pathways.
abstract: Innate immune signaling associated with Toll-like receptors (TLRs) is a key pathway involved in the progression of liver fibrosis. In this study, we reported that TLR2 is required for hepatic fibrogenesis induced by carbon tetrachloride (CCl4). After CCl4 treatment, TLR2(-/-) mice had reduced liver enzyme levels, diminished collagen deposition, decreased inflammatory infiltration and impaired activation of hepatic stellate cells (HSCs) than wild type (WT) mice. Furthermore, after CCl4 treatment, TLR2(-/-) mice demonstrated downregulated expression of profibrotic and proinflammatory genes and impaired mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-κB) activation than WT mice. Collectively, our data indicate that TLR2 deficiency protects against CCl4-induced liver fibrosis.
authors.affiliation: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Gene Research Center, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Ji
authors.affiliation: Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Ruyi
authors.initials: R
authors.lastname: Xue
authors.affiliation: Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Tang
authors.affiliation: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Gene Research Center, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Weibin
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Hu
authors.affiliation: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Gene Research Center, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Xijun
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Gene Research Center, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Peng
authors.affiliation: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Gene Research Center, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Gu
authors.affiliation: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Gene Research Center, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China. Electronic address: SheChen@fudan.edu.cn.
authors.forename: She
authors.initials: S
authors.lastname: Chen
authors.affiliation: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Gene Research Center, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China. Electronic address: Zhangsi@fudan.edu.cn.
authors.forename: Si
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D055786:Gene Knockout Techniques; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000172:deficiency* / Q000235:genetics*
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D003094:Collagen; D002251:Carbon Tetrachloride; D020928:Mitogen-Activated Protein Kinases
keywords: Carbon tetrachloride; Hepatic stellate cell; Liver fibrosis; NF-κB; Toll like receptor 2; mitogen-activated protein kinases