TGF-β1 contributes to the hepatic inflammation in animal models with nonalcoholic steatohepatitis by Smad3/TLR2 signaling pathway

• Published in: Molecular immunology Vol. 152; pp. 129 - 139
• Main Authors: Chen, Qian, Yi, Jing, Liu, Fangtong, Li, Jing, Lu, Kaikai, Wang, Xuan, Zhang, Fujun, Li, Ya, Wu, Litao, Yang, Xudong, Lu, Shemin, Li, Dongmin
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.12.2022
• Subjects: Nonalcoholic steatohepatitis (NASH); Smad3; Toll-like receptor 2 (TLR2); Transforming growth factor-β1 (TGF-β1); NAFLD; TNFα; IL6; Smad3; Toll-like receptor 2 (TLR2); Transforming growth factor-β1 (TGF-β1); HFD; HFHC; TGF-β1; NASH; TLR2; Nonalcoholic steatohepatitis (NASH)
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2022.10.014

Non-alcoholic fatty liver disease (NAFLD) is increasingly affecting human health and the economy worldwide due to various factors. Here, we found that the expression of TGF-β1 and TLR2 was significantly up-regulated in liver samples from both rats and mice nonalcoholic steatohepatitis (NASH) models. By constructing corresponding cell model, we found that TGF-β1 challenge can positively regulate the expression of TLR2 and p-Smad2/3, and the dual luciferase reporter gene system and EMSA assay confirmed the existence of Smad3 binding site (−916 ∼ −906) in the promoter region of TLR2. The overexpression and interference changes of Smad2/3 further verified the above experimental results. Taken together, these findings suggest that TGF-β1 promotes TLR2 transcription and its target gene expression via Smad3, leading to malignant exacerbation of liver inflammation in NASH, which provides new insights into the treatment of NASH. •The expression of TGF-β1 and TLR2 was significantly up-regulated in liver samples from both the rats and mice NASH models.•TGF-β1 positively regulate the expression of TLR2 and its downstream inflammatory molecules, as well as p-Smad2/3, Smad4.•TGF-β1 promotes TLR2 transcription and its target gene expression via Smad3, but not Smad2.