NS5ATP9 Suppresses Activation of Human Hepatic Stellate Cells, Possibly via Inhibition of Smad3/Phosphorylated-Smad3 Expression
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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.
KEY WORDSNS5ATP9 liver fibrosis LX-2 cells TGF-β1 extracellular matrix
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.
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).
- 14.Emanuele, M.J., A. Ciccia, A.E. Elia, and S.J. Elledge. 2011. Proliferating cell nuclear antigen (PCNA)-associated KIAA0101/PAF15 protein is a cell cycle-regulated anaphase-promoting complex/cyclosome substrate. Proceedings of the National Academy of Sciences of the United States of America 108: 9845–9850.CrossRefPubMedCentralPubMedGoogle Scholar
- 16.Quan M, Liu S, Li G, et al. 2013. A functional role for NS5ATP9 in the induction of HCV NS5A-mediated autophagy. J Viral Hepat, accepted.Google Scholar
- 31.Wang, Q., Y. Wang, Y. Li, X. Gao, S. Liu, and J. Cheng. 2013. NS5ATP9 contributes to inhibition of cell proliferation by hepatitis C virus (HCV) nonstructural protein 5A (NS5A) via MEK/extracellular signal regulated kinase (ERK) pathway. International Journal of Molecular Sciences 14: 10539–10551.CrossRefPubMedCentralPubMedGoogle Scholar