Wnt signaling enhances the activation and survival of human hepatic stellate cells.
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.
Myung
Sun Jung
SJ
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Yoon
Jung-Hwan
JH
Gwak
Geum-Youn
GY
Kim
Won
W
Lee
Jeong-Hoon
JH
Kim
Kang Mo
KM
Shin
Chan Soo
CS
Jang
Ja June
JJ
Lee
Sung-Hee
SH
Lee
Soo-Mi
SM
Lee
Hyo-Suk
HS
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
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