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.
MeSH terms
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Amino Acid Sequence
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Apoptosis / genetics
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Cell Survival
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Cells, Cultured
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Hepatocytes / cytology*
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Hepatocytes / drug effects
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Humans
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / metabolism
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Liver / cytology*
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Liver / metabolism*
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Liver Cirrhosis / etiology*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Molecular Sequence Data
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Sequence Homology, Amino Acid
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Signal Transduction / physiology
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TNF-Related Apoptosis-Inducing Ligand / pharmacology
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Transfection
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Wnt Proteins / metabolism
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Wnt Proteins / pharmacology
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Wnt Proteins / physiology*
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Wnt3 Protein
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Wnt3A Protein
Substances
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Intercellular Signaling Peptides and Proteins
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Membrane Proteins
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SFRP1 protein, human
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TNF-Related Apoptosis-Inducing Ligand
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TNFSF10 protein, human
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WNT3A protein, human
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Wnt Proteins
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Wnt3 Protein
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Wnt3A Protein