Recombinant human histidine triad nucleotide-binding protein 1 attenuates liver fibrosis induced by carbon tetrachloride in rats.

Abstract

It is currently thought that the transforming growth factor-β (TGF-β)/Smad signaling pathway acts as a central pathway leading to liver fibrosis, and that the aberrant Wnt/β-catenin signaling pathway also plays a vital role in the development of liver fibrosis. There is evidence that the histidine triad nucleotide-binding protein 1 (Hint1) was capable of inhibiting these two pathways. However, little data regarding the effects of Hint1 on liver fibrosis exists. Thus, we sought to investigate whether the recombinant human Hint1 protein (rhHint1) was capable of attenuating liver fibrosis induced by carbon tetrachloride (CCl4) in rats and the possible underlying mechanism(s) of action. In the present study, purified rhHint1 was obtained using genetic engineering technology. Liver fibrosis was induced in male Sprague-Dawley (SD) rats by the subcutaneous injection of CCl4. The rats were randomly divided into the normal control, the liver fibrosis model and the rhHint1 (doses, 50 and 100 µg/kg)‑treated groups. Following four weeks of treatment, the rhHint1-treated rats exhibited significantly reduced liver fibrosis upon histopathological analysis and lower levels of hydroxyproline. Furthermore, rhHint1 inhibited the expression of α-smooth muscle actin (α-SMA) in the liver tissues. Additionally, rhHint1 lowered the gene expression levels of TGF-β1/Smad3 and β-catenin/cyclin D1, whereas it increased the gene expression levels of Smad7. In conclusion, the results of this study indicated that rhHint1 is capable of attenuating CCl4-induced liver fibrosis by simultaneously targeting multiple pathogenic pathways, which may be developed as a new treatment for liver fibrosis.

• Authors: Fei Wu, Shaofang Huang, Nanlan Zhu, Wei Liu, Yanan Zhang, Yongwen He
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 8 Issue 4 Pg. 1023-8 (Oct 2013) ISSN: 1791-3004 [Electronic] Greece
• PMID: 23934318 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HINT1 protein, human
• Nerve Tissue Proteins
• Recombinant Proteins
• Smad3 Protein
• Smad3 protein, rat
• Smad7 Protein
• Smad7 protein, rat
• Tgfb1 protein, rat
• Transforming Growth Factor beta1
• Carbon Tetrachloride
• Hydroxyproline

Topics

• Animals
• Carbon Tetrachloride
• Hepatic Stellate Cells (drug effects, metabolism)
• Humans
• Hydroxyproline (metabolism)
• Liver (drug effects, metabolism, pathology)
• Liver Cirrhosis (chemically induced, drug therapy)
• Male
• Nerve Tissue Proteins (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Recombinant Proteins (pharmacology, therapeutic use)
• Smad3 Protein (genetics, metabolism)
• Smad7 Protein (genetics, metabolism)
• Transforming Growth Factor beta1 (genetics, metabolism)