title: NS5ATP13 Promotes Liver Fibrogenesis Via Activation of Hepatic Stellate Cells.
abstract: Liver fibrosis is a reversible wound-healing response to any etiology of chronic hepatic injuries. Activation of hepatic stellate cells (HSCs) is the key event in liver fibrogenesis. Generally, persistent activation and proliferation of HSCs results in liver fibrosis progression, while primary mechanisms of liver fibrosis resolution are apoptosis and reversion to a quiescent phenotype of activated HSCs. NS5ATP13 (HCV NS5A-transactivated protein 13) is involved in nucleologenesis and tumorigenesis, but its role in liver fibrosis and HSC activation remains unclear. This study found that NS5ATP13 was upregulated in both fibrotic liver tissues and activated human HSCs induced by TGF-β1. Moreover, NS5ATP13 enhanced extracellular matrix (ECM) production and HSC activation, with or without TGF-β1 treatment, likely involving the TGF-β1/Smad3 signaling pathway. Additionally, NS5ATP13 boosted HSC proliferation by inhibiting cell apoptosis. Furthermore, HCV NS5A promoted the profibrogenic effect of NS5ATP13 partly through TGF-β1 and NF-κB p65 (RelA) upregulation. Meanwhile, NS5ATP13 was required for the pro-fibrogenic effect of NF-κB. Moreover, NS5ATP13 and NF-κB phosphorylation as well as HSC activation were reduced by CX-4945, a CK2 specific inhibitor. These findings indicated that NS5ATP13 acts as a profibrogenic factor, providing a potential target for antifibrotic therapies. J. Cell. Biochem. 118: 2463-2473, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, 100015, China.
authors.forename: Yaru
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, 100015, China.
authors.forename: Shunai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, 100015, China.|Beijing Ditan Hospital, Teaching Hospital of Peking University, Beijing, 100015, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Han
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, 100015, China.
authors.forename: Hongping
authors.initials: H
authors.lastname: Lu
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, 100015, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, 100015, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, 100015, China.|The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China.
authors.forename: Kelbinur
authors.initials: K
authors.lastname: Tursun
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, 100015, China.
authors.forename: Zhongshu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, 100015, China.|Beijing Ditan Hospital, Teaching Hospital of Peking University, Beijing, 100015, China.
authors.forename: Shenghu
authors.initials: S
authors.lastname: Feng
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, 100015, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009287:Naphthyridines / Q000494:pharmacology; D010619:Phenazines; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology
chemical_list: D016328:NF-kappa B; D009287:Naphthyridines; D010619:Phenazines; D011506:Proteins; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; C555142:silmitasertib
keywords: CX-4945; HEPATIC STELLATE CELLS; LIVER FIBROSIS; NF-κB; NS5ATP13; TGF-β1