Effect of Fibroblast Growth Factor 21 on the Expression of <i>TLR4</i> and <i>BAMBI</i> Genes in Cholesterol-Treated Human Hepatic Stellate Cells

AuthorElham Shakerianen
AuthorNarges Mohammadtaghvaeien
AuthorZohre Askarien
AuthorReza Afarinen
OrcidElham Shakerian [0000-0001-5437-0056]en
OrcidNarges Mohammadtaghvaei [0000-0003-4175-8099]en
OrcidReza Afarin [0000-0003-3644-0668]en
Issued Date2021-09-30en
AbstractBackground: Activated hepatic stellate cells (HSCs) are the primary mediators in the progression of hepatic fibrosis. The activation of toll-like receptor 4 (TLR4) signaling leads to the downregulation of the transmembrane inhibitory transforming growth factor-beta (TGF-β) pseudoreceptor BMP and activin membrane-bound inhibitor (BAMBI) on HSCs. Fibroblast growth factor 21 (FGF21) is a natural secretory protein in the body with effects, such as the reduction of fat accumulation and oxidation of lipids; however; no study has investigated FGF21 ability to prevent the progression of liver fibrosis. Objectives: This study aimed to examine the beneficial effects of FGF21 to reduce cholesterol-activated human HSCs. Methods: The human HSCs were incubated in media containing different concentrations of cholesterol, including 25, 50, 75, 100, 125, and 150 μM, for 24 h and then incubated with FGF21 for 24 h. Total ribonucleic acids were extracted and reversely transcribed into complementary deoxyribonucleic acid. A quantitative real-time polymerase chain reaction was performed in this study. Results: The results showed that the messenger ribonucleic acid (mRNA) expression of TGF-β, collagen, type I, alpha 1 (collagen1α), and TLR4 genes increased significantly in the presence of cholesterol (75 and 100 μM), compared to that of the control group (* P < 0.05, ** P < 0.01, and *** P < 0.001); nevertheless, the mRNA expression of the BAMBI gene significantly reduced, compared to that of the control group (* P < 0.05). The FGF21 significantly reduced the mRNA expression of TGF-β, collagen1α, and TLR4 genes (# P < 0.05). The mRNA expression of the BAMBI gene significantly increased with FGF21 (# P < 0.05). Conclusions: It was concluded that the treatment with FGF21 reduces the cholesterol-activated HSCs by decreasing the mRNA expression of the TLR4, TGF-β, and collagen1α genes and increasing the mRNA expression of the BAMBI gene.en
DOIhttps://doi.org/10.5812/jjcmb.113672en
PublisherBrieflandsen
TitleEffect of Fibroblast Growth Factor 21 on the Expression of <i>TLR4</i> and <i>BAMBI</i> Genes in Cholesterol-Treated Human Hepatic Stellate Cellsen
TypeResearch Articleen

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