Canonical Wnt signaling maintains the quiescent stage of hepatic stellate cells
- Clinic of Gastroenterology, Hepatology and Infectiology, Heinrich-Heine-University, Moorenstrasse 5, 40225 Duesseldorf (Germany)
It is well known that hepatic stellate cells (HSC) develop into cells, which are thought to contribute to liver fibrogenesis. Recent data suggest that HSC are progenitor cells with the capacity to differentiate into cells of endothelial and hepatocyte lineages. The present study shows that {beta}-catenin-dependent canonical Wnt signaling is active in freshly isolated HSC of rats. Mimicking of the canonical Wnt pathway in cultured HSC by TWS119, an inhibitor of the glycogen synthase kinase 3{beta}, led to reduced {beta}-catenin phosphorylation, induced nuclear translocation of {beta}-catenin, elevated glutamine synthetase production, impeded synthesis of {alpha}-smooth muscle actin and Wnt5a, but promoted the expression of glial fibrillary acidic protein, Wnt10b, and paired-like homeodomain transcription factor 2c. In addition, canonical Wnt signaling lowered DNA synthesis and hindered HSC from entering the cell cycle. The findings demonstrate that {beta}-catenin-dependent Wnt signaling maintains the quiescent state of HSC and, similar to stem and progenitor cells, influences their developmental fate.
- OSTI ID:
- 21043636
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 367, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2007.12.085; PII: S0006-291X(07)02746-5; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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