Histone deacetylase inhibitor suberoylanilide hydroxamic acid alleviates liver fibrosis by suppressing the transforming growth factor-β1 signal pathway

• Published in: Hepatobiliary & pancreatic diseases international 2018-10, Vol.17 (5), p.423-429
• Main Authors: Wang, Yao, Zhao, Lei, Jiao, Fang-Zhou, Zhang, Wen-Bin, Chen, Qian, Gong, Zuo-Jiong
• Format: Article
• Language: English
• Subjects: Acetylation; Analysis of Variance; Animals; Biopsy, Needle; Blotting, Western; Disease Models, Animal; Histone Deacetylase Inhibitors - pharmacology; Immunohistochemistry; Liver Cirrhosis - chemically induced; Liver Cirrhosis - drug therapy; Liver Cirrhosis - pathology; Liver fibrosis; Male; Molecular Targeted Therapy - methods; Random Allocation; Rats; Rats, Sprague-Dawley; Signal Transduction - drug effects; Smad Proteins - metabolism; Suberoylanilide hydroxamic acid; Transforming Growth Factor beta1 - drug effects; Transforming growth factor-β1; Vorinostat - pharmacology
• ISSN: 1499-3872
• DOI: 10.1016/j.hbpd.2018.09.013

Histone deacetylases (HDACs) inhibitors are new anti-fibrotic drugs that inhibit the activity of hepatic stellate cells. The present study focused on the anti-fibrotic function of HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) by suppressing transforming growth factor-β1 (TGF-β1) signaling. Male Sprague-Dawley rats were used to induce liver fibrosis with carbon tetrachloride (CCl4) and LX2 cell (human hepatic stellate cell line) was stimulated by TGF-β1. Both animals and cells were treated with SAHA. The Smad7 and connective tissue growth factor (CTGF) mRNA levels were detected by real-time polymerase chain reaction (PCR). Western blotting was used to examine the protein levels of CTGF, Histone H3 (H3), Smad7, Smad2/3, Acetyl-Histone H3 (AH3), HDAC2, α-smooth muscle actin (α-SMA), HDAC6, p-Smad2/3 and HDAC8. In addition, the TGF-β1 and liver enzyme levels from rat serum were detected. Histopathological changes were examined by hematoxylin and eosin (HE), Sirius red and Masson trichrome staining. The α-SMA expression was detected by immumohistochemical staining. Compared with control group, the TGF-β1 and liver enzyme levels from rat serum, together with the mRNA levels of CTGF and protein levels of CTGF, HDAC2, α-SMA, HDAC6, p-Smad2/3 and HDAC8 were elevated in fibrotic rats (P