Premium
Activation of the Wnt/β‐catenin pathway leads to enhanced proliferation and liver regeneration in mice
Author(s) -
NejakBowen Kari Nichole,
Thompson Michael,
Monga Satdarshan
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.236.1
Subject(s) - wnt signaling pathway , cyclin d1 , liver regeneration , regeneration (biology) , catenin , cell growth , biology , hepatocyte , cell cycle , microbiology and biotechnology , cyclin , zebrafish , chemistry , endocrinology , medicine , signal transduction , cell , biochemistry , in vitro , gene
An important role for β‐catenin in liver regeneration is observed in mice, rats and more recently in zebrafish and humans. In order to elucidate any stimulatory impact of β‐catenin on liver regeneration, we utilized transgenic (TG) mice that overexpress β‐catenin under an albumin promoter/enhancer in FVB strain. Using the partial hepatectomy (PHx) model of liver regeneration, we found a dramatic increase in cell proliferation in TG mice as compared to WT at 40H after PHx, before the onset of proliferation in WT FVB mice that occurs at 72H. Coincident with the earlier onset of proliferation, β‐catenin translocates to the nucleus at 40H post‐PHx in TGs, whereas this translocation does not occur until 72H in WT. Analysis of cyclin D1 expression by Western blotting showed that levels of this cell‐cycle regulator are several‐fold higher in TG than in WT at 40H. We tested if hydrodynamic delivery of Wnt‐1 naked DNA could also impact regeneration in WT mice. We observed a significant increase in total Wnt‐1, β‐catenin, glutamine synthetase, cyclin‐D1 and PCNA in the Wnt‐1 and not the control plasmid‐injected mice, similar to that seen in the β‐catenin overexpressing TG mice. In conclusion, stimulation of Wnt/β‐catenin signaling induces liver regeneration through induction of such downstream targets as cyclin‐D1, and thus might have implications in regenerative medicine.