title: Wnt signaling enhances the activation and survival of human hepatic stellate cells.
abstract: Wnt signaling was implicated in pulmonary and renal fibrosis. Since Wnt activity is enhanced in liver cirrhosis, Wnt signaling may also participate in hepatic fibrogenesis. Thus, we determined if Wnt signaling modulates hepatic stellate cell (HSC) activation and survival. Wnt3A treatment significantly activated human HSCs, while this was inhibited in secreted frizzled-related protein 1 (sFRP1) overexpressing cells. Wnt3A treatment significantly suppressed TRAIL-induced apoptosis in control HSCs versus sFRP1 over-expressing cells. Particularly, caspase 3 was more activated in sFRP1 over-expressing cells following TRAIL and Wnt3A treatment. These observations imply that Wnt signaling promotes hepatic fibrosis by enhancing HSC activation and survival.
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sun Jung
authors.initials: SJ
authors.lastname: Myung
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Yoon
authors.forename: Geum-Youn
authors.initials: GY
authors.lastname: Gwak
authors.forename: Won
authors.initials: W
authors.lastname: Kim
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Kang Mo
authors.initials: KM
authors.lastname: Kim
authors.forename: Chan Soo
authors.initials: CS
authors.lastname: Shin
authors.forename: Ja June
authors.initials: JJ
authors.lastname: Jang
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Soo-Mi
authors.initials: SM
authors.lastname: Lee
authors.forename: Hyo-Suk
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics; D002470:Cell Survival; D002478:Cells, Cultured; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000209:etiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology; D014162:Transfection; D051153:Wnt Proteins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins; C505653:TNFSF10 protein, human; C555510:WNT3A protein, human