Effect of histone deacetylase inhibitor on epithelial-mesenchymal transition of liver fibrosis.

Autor: Ramzy MM; Department of Biochemistry, Faculty of Medicine, Minia University, Egypt., Abdelghany HM; Department of Biochemistry, Faculty of Medicine, Minia University, Egypt., Zenhom NM; Department of Biochemistry, Faculty of Medicine, Minia University, Egypt., El-Tahawy NF; Department of Histology and Cell Biology, Faculty of Medicine, Minia University, Egypt.
Jazyk: angličtina
Zdroj: IUBMB life [IUBMB Life] 2018 Jun; Vol. 70 (6), pp. 511-518. Date of Electronic Publication: 2018 Mar 30.
DOI: 10.1002/iub.1742
Abstrakt: Liver fibrosis is an excessively reversible wound healing process and the fibrotic disorder is the activation of hepatic stellate cell that requires extensive alterations in gene expression. As reversible deacetylation of histone proteins modulate gene expression, we examined the effect of valproic acid (VPA) as selective histone deacetylase inhibitor on CCl-4 induced liver fibrosis. Thirty rats were divided into three equal groups; control group, fibrotic group and VPA-treated group. The rats were sacrificed after 6 weeks of liver fibrosis induction. The histopathological effect on liver tissue was examined. The expression of α-SMA and Smad-4 mRNA and serum levels of TGF-β1, alanine aminotransferase, and aspartate aminotransferase were determined. Treatment of rats with VPA attenuated carbon tetrachloride-induced liver fibrosis. Moreover, α-SMA and Smad-4 expression was repressed under VPA treatment and both serum TGF-β1 and liver enzymes were significantly decreased. The histone deacetylase inhibitor-1 VPA inhibits the epithelial-mesenchymal transition and affects hepatic stellate cell activation during liver fibrosis through downregulation of Smad4 and α-SMA expression which may serve as a promising agent in liver fibrosis treatment. © 2018 IUBMB Life, 70(6):511-518, 2018.
(© 2018 International Union of Biochemistry and Molecular Biology.)
Databáze: MEDLINE
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