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NS5ATP9 Suppresses Activation of Human Hepatic Stellate Cells, Possibly via Inhibition of Smad3/Phosphorylated-Smad3 Expression

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Abstract

Activation of hepatic stellate cell (HSC) is the central event in liver fibrosis. NS5ATP9 is related to many malignant tumors, but little is known about its function in HSC activation. The aim of this study is to investigate the role of NS5ATP9 in HSC activation in vitro. Genes related to liver fibrosis were detected after NS5ATP9 overexpression or silencing with or without transforming growth factor (TGF)-β1 stimulation in the human HSCs by real-time polymerase chain reaction and western blotting. Cell proliferation, migration, and apoptosis were tested, and the mechanisms underlying the effect of NS5ATP9 on HSC activation were studied. We showed that NS5ATP9 suppressed HSC activation and collagen production, with or without TGF-β1 induction. Also, NS5ATP9 inhibited cell proliferation and migration and promoted apoptosis. Furthermore, NS5ATP9 reduced basal and TGF-β1-mediated Smad3/phosphorylated-Smad3 expression. The existence of a physical complex between NS5ATP9 and Smad3 was illustrated. NS5ATP9 suppresses HSC activation, extracellular matrix production, and promotes apoptosis, in part through reducing Smad3/phosphorylated-Smad3 expression.

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ACKNOWLEDGMENTS

We thank Hongshan Wei and Guoli Li, Beijing Key Laboratory of Emerging Infectious Diseases; Dkewr Peng Wang, Liang Zhang, Lei Sun, and Xingang Zhou, Department of Pathology, Beijing Ditan Hospital, Capital Medical University; and Dr. Min Li, Department of Infectious Disease, the First Affiliated Hospital of Lanzhou University, for the supportive discussions and technical assistance.

Conflict of Interest

The authors declare no conflicts of interest related to this work.

Financial Support

This work was supported by grants from the National Natural Science Foundation of China (nos. 81470863), the Healthy Talent Leadership Programs of Beijing (nos. 2009-1-09), and the National Key Subjects Foundation of Infectious Diseases during the Five-Year Plan Period of China (nos. 2012ZX10002003, 2013ZX10002005, and 2012ZX10004904).

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Authors and Affiliations

  1. Institutes of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, 8 East Jingshun St., Beijing, 100015, China

    Mengran Zhang, Jinqian Zhang, Shunai Liu, Qi Wang & Jun Cheng

  2. Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, 100015, China

    Mengran Zhang, Jinqian Zhang, Shunai Liu, Qi Wang, Min Quan & Jun Cheng

  3. Department of Infectious Disease, Affiliated Hospital of Putian College, Fujian, 351100, China

    Guoxian Lin & Rongxian Qiu

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  1. Mengran Zhang
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  2. Jinqian Zhang
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  7. Min Quan
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Correspondence to Jun Cheng.

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Mengran Zhang and Jinqian Zhang contributed equally to this work

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Zhang, M., Zhang, J., Liu, S. et al. NS5ATP9 Suppresses Activation of Human Hepatic Stellate Cells, Possibly via Inhibition of Smad3/Phosphorylated-Smad3 Expression. Inflammation 38, 278–289 (2015). https://doi.org/10.1007/s10753-014-0031-y

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