Canonical Wnt signaling maintains the quiescent stage of hepatic stellate cells.

Abstract:

: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 3beta, 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.

authors

Kordes C,Sawitza I,Häussinger D

doi

10.1016/j.bbrc.2007.12.085

subject

Has Abstract

pub_date

2008-02-29 00:00:00

pages

116-23

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(07)02746-5

journal_volume

367

pub_type

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