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Submitted: 05 Aug 2021
Accepted: 27 Nov 2021
ePublished: 02 Jan 2022
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Immunopathol Persa. 2023;9(1): e29268.
doi: 10.34172/ipp.2022.29268
  Abstract View: 163
  PDF Download: 123

Original

Alleviative effects of fibroblast growth factor 21 on fibrogenic genes expression in the fructose activated hepatic stellate cells, an in vitro study

Elham Shakerian 1,2 ORCID logo, Hamid Yaghooti 1,3 ORCID logo, Alireza Kheirollah 4 ORCID logo, Narges Mohammadtaghvaei 1* ORCID logo

1 Hyperlipidemia Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2 Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
3 Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
4 Department of Biochemistry, Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
*Corresponding Author: Correspondence to Narges Mohammadtaghvaei, Email: mohammadtaghvaei-n@ ajums.ac.ir, , Email: ntaghvaiie@gmail.com

Abstract

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.



Citation: Shakerian E, Yaghooti H, Kheirollah A, Mohammadtaghvaei N. Alleviative effects of fibroblast growth factor 21 on fibrogenic genes expression in the fructose activated hepatic stellate cells, an in vitro study. Immunopathol Persa. 2023;9(1):e29268. DOI:10.34172/ ipp.2022.29268.
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