title: NS5ATP9 suppresses activation of human hepatic stellate cells, possibly via inhibition of Smad3/phosphorylated-Smad3 expression.
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.
authors.affiliation: Institutes of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, 8 East Jingshun St., Beijing, 100015, China, zmr1984@aliyun.com.
authors.forename: Mengran
authors.initials: M
authors.lastname: Zhang
authors.forename: Jinqian
authors.initials: J
authors.lastname: Zhang
authors.forename: Shunai
authors.initials: S
authors.lastname: Liu
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Guoxian
authors.initials: G
authors.lastname: Lin
authors.forename: Rongxian
authors.initials: R
authors.lastname: Qiu
authors.forename: Min
authors.initials: M
authors.lastname: Quan
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
mesh_terms: D002352:Carrier Proteins / Q000096:biosynthesis* / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051900:Smad3 Protein / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C425208:PCLAF protein, human; C497790:SMAD3 protein, human; D051900:Smad3 Protein