Nickan Research Institute Immunopathologia Persa 2423-8015 9 1 2023 01 01 Alleviative effects of fibroblast growth factor 21 on fibrogenic genes expression in the fructose activated hepatic stellate cells, an in vitro study e29268 e29268 10.34172/ipp.2022.29268 EN Elham Shakerian https://orcid.org/0000-0001-5437-0056 Hamid Yaghooti https://orcid.org/0000-0002-7517-6807 Alireza Kheirollah https://orcid.org/0000-0002-8235-8190 Narges Mohammadtaghvaei https://orcid.org/0000-0003-4175-8099 Journal Article 10.34172/ipp.2022.29268 2021 08 05 2021 11 27 Introduction: Liver fibrosis occurs through hepatic stellate cells (HSCs) activation during chronic liver injury. Cytokines especially transforming growth factor-β (TGF-β), activate HSCs by an autocrine effect. The activated HSCs generate more α-smooth muscle actin (α-SMA) and Collagen1. The activation of human HSCs by high fructose concentrations has been confirmed. Fibroblast growth factor 21 (FGF21) as a hepatic hormone possesses favorable metabolic effects, but its effect on activated HSCs and the process of fibrogenesis have not been studied yet. Objectives: In this study, we evaluated the effect of FGF21 on suppressing the fructose-activated human HSCs and its effect on the TGF-β/ Smad3 signaling pathway. Materials and Methods: The LX-2 cells were grown in the presence of high fructose concentrations (25 and 30 mM) for 48 hours for activation and then were treated with FGF21. Quantitative real-time polymerase chain reaction (real-time PCR) was performed to measure the expression of fibrogenic genes and western blotting to analyze the TGF-β signaling. Results: Our results showed increased levels of mRNA expression of αSMA, collagen1, and TGF-β genes and smad3 phosphorylation in fructose-activated HSCs. FGF21 treatment significantly attenuated the induced fibrogenic gene expression and smad3 phosphorylation. Conclusion: High fructose leads to fibrogenic pathways in the liver by activating HSCs and increasing TGF-β signaling. FGF21 is effective in reducing fibrogenesis in activated HSCs through downregulating the TGF-β/smad3 signaling and fibrogenic gene expression. Therefore, FGF21 may provide anti-fibrotic properties in liver fibrosis.