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Wnt/β‐Catenin pathway is critical in hepatic oval cell activation in rats.
Author(s) -
Apte Udayan,
Cui Shanshan,
Liu Bowen,
Thompson Michael,
Zeng Gang,
Cieply Benjamin,
Stolz Donna B.,
Monga Satdharshan P.S.
Publication year - 2007
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.21.5.a70-c
Subject(s) - wnt signaling pathway , liver regeneration , hepatocyte , catenin , colocalization , cell growth , microbiology and biotechnology , biology , cell , regeneration (biology) , chemistry , medicine , signal transduction , in vitro , biochemistry
Hepatic oval cells are the facultative stem cells in the adult liver, activated during liver regeneration if the innate hepatocyte proliferation is inhibited. Based on its involvement in liver cancer and regeneration, we investigated the role of Wnt/β‐catenin pathway in hepatic oval cell activation. Oval cell activation was studied in male F344 rats using 2‐acetylaminofluorine treatment followed by 2/3rd partial hepatectomy (PHX) 7 days later. Oval cell activation in the liver was studied at 5, 10 and 20 days after PHX. Extensive oval cell activation was observed within 5 days with peak oval cell proliferation at 10 day post‐PHX as indicated by H&E, PCNA analysis. Significant β‐catenin induction in oval cells as indicated by β‐catenin and Thy‐1 colocalization, was observed at 5 days post‐PHX with extensive cytoplasmic stabilization and nuclear localization at 10 days post‐PHX. The primary mechanism of β‐catenin activation was down regulation of GSK‐3β. Additionally, induction in Wnt‐1, an activator of β‐catenin and decrease in WIF‐1, an inhibitor of Wnt‐1, was observed at 5, and 10 days after PHX. Immunoflourescent colocalization indicated increase in β‐catenin complex with E‐cadherin as well as c‐Met at 5 and 20 days post‐PHX while decrease at 10 days post‐PHX. Taken together, these data indicate that β‐catenin activation plays a significant role in activation and proliferation initially, and differentiation into hepatocytes at later stages.