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Inhibition of hepatic stellate cell activation and liver fibrosis by fat-specific protein 27

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Abstract

In order to explore the effects of fat-specific protein 27 (Fsp27) on regulation of hepatic stellate cell (HSC) activation and liver fibrosis. HSCs were isolated from rat liver tissues and cultivated in vitro for gene expression and lentivirus infection. CCK-8 cell viability assay, immunofluorescence staining, qRT-PCR, and western blot assays were used to assess phenotypic changes and gene expression in HSCs. The rat liver fibrosis model was produced by intraperitoneal injection of carbon tetrachloride for assessing the effects of Fsp27 in the rat liver. Gene expression was then detected by immunohistochemistry and ELISA assays. The results of the study showed that Fsp27 was constitutively expressed in primary quiescent HSCs, but was absent in activated HSCs. Ectopic expression of Fsp27 significantly inhibited HSC proliferation and activation, as well as expression of α-smooth muscle actin. Fsp27 expression also significantly reduced collagen I production and matrix metalloproteinases 2 protein levels, and to a lesser degree, reduced tissue inhibitors of metalloproteinases 1 expression. In vivo data showed that ectopic expression of Fsp27 protein significantly reduced levels of hydroxyproline in liver tissue, and decreased serum levels of collagen III and hyaluronic acid, which in turn, suppressed liver fibrosis in rats. From these findings, it can be concluded that Fsp27 expression suppressed HSC activation in vitro and liver fibrogenesis in vivo. Further studies are needed to explore whether expression of Fsp27 can be selected as a potential novel strategy for anti-fibrotic therapy against liver fibrosis.

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Acknowledgments

This study was supported in part by a grant from Zhejiang Provincial Top Key Discipline in Surgery. The authors thank their colleagues in the Animal Experimental Center of Wenzhou Medical College for their assistance. The authors also thank the Medjaden Bioscience Limited, Hong Kong, China for improving the English of this manuscript.

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  1. Department of Hepatobiliary-Pancreatic Surgery, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, 325000, China

    Fuxiang Yu, Longfeng Su, Shiqiang Ji, Shengchu Zhang, Panpan Yu, Yihu Zheng & Qiyu Zhang

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  1. Fuxiang Yu
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  2. Longfeng Su
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  3. Shiqiang Ji
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Correspondence to Qiyu Zhang.

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Yu, F., Su, L., Ji, S. et al. Inhibition of hepatic stellate cell activation and liver fibrosis by fat-specific protein 27. Mol Cell Biochem 369, 35–43 (2012). https://doi.org/10.1007/s11010-012-1366-z

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  • DOI: https://doi.org/10.1007/s11010-012-1366-z

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