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Hepatocyte‐targeted Overexpresssion of Glypican 3 in Mice Suppresses Hepatocyte Proliferation and Hepatomegaly after Phenobarbital Administration
Author(s) -
Lin ChihWen,
Liu Bowen,
Donthamsetty Shashikiran,
Orr Anne,
Bowen William C,
Kang LiangI,
Mars Wendy M,
Michalopoulos George K
Publication year - 2011
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.25.1_supplement.998.6
Subject(s) - hepatocyte , phenobarbital , medicine , liver regeneration , endocrinology , glypican 3 , transgene , cell growth , chemistry , biology , microbiology and biotechnology , regeneration (biology) , immunohistochemistry , gene , biochemistry , in vitro
Glypican 3 (GPC3) belongs to a family of GPI‐anchored, cell‐surface HSPGs. GPC3 is overexpressed in HCC. Loss‐of‐function mutations of GPC3 result in SGBS by overgrowth of multiple organs. Our previous study showed that in GPC3 transgenic (TG) mice, hepatocyte overexpression of GPC3 suppresses hepatocyte proliferation and liver regeneration and alters gene expression. This study investigates the role of GPC3 in hepatocyte proliferation and liver enlargement induced by phenobarbital (PB). WT and GPC3 TG mice were given 0.1 % PB in drinking water for 10 days. Livers were harvested on 1, 3, 5, and 10 days during PB administration. In WT mice, the liver weight was double as compared to day 0 at day 5. In TG mice, the liver weight was a little larger as compared to day 0 at day 5 (1.3 times). In TG mice, the hepatocyte proliferation by Ki67 positive nuclear staining was significantly suppressed at day 3 compared with WT mice after PB administration. An increase of GPC3 protein levels was observed in TG mice compared with WT mice. Moreover, gene array analysis revealed a series of changes in the gene expression profile in TG mice. After PB administration, a panel of cell cycle related genes are either up‐ or down‐regulated, as confirmed by western blotting. In summary, hepatocyte overexpression of GPC3 suppresses proliferative response not only to liver regeneration but also to xenobiotic chemical mitogens, such as PB.