GSK-3? suppresses the proliferation of rat hepatic oval cells through modulating Wnt/?-catenin signaling pathway.

ABSTRACT: Glycogen synthase kinase 3? (GSK-3?) plays a crucial role in hepatic biology, including liver development, regeneration, proliferation and carcinogenesis. In this study we investigated the role of GSK-3? in regulation of growth of hepatic oval cells in vitro and in liver regeneration in partially hepatectomized rats.WB-F344 cells, the rat hepatic stem-like epithelial cells, were used as representative of oval cells. Cell viability was examined using a WST-8 assay. The cells were transfected with a recombinant lentivirus expressing siRNA against GSK-3? (GSK-3?RNAiLV) or a lentivirus that overexpressed GSK-3? (GC-GSK-3?LV). Adult rats underwent partial (70%) hepatectomy, and liver weight and femur length were measured at d 7 after the surgery. The expression of GSK-3?, phospho-Ser9-GSK-3?, ?-catenin and cyclin D1 was examined with immunoblotting assays or immunohistochemistry.Treatment of WB-F344 cells with the GSK-3? inhibitor SB216763 (5 and 10 ?mol/L) dose-dependently increased the levels of phospho-Ser9-GSK-3?, but not the levels of total GSK-3?, and promoted the cell proliferation. Knockout of GSK-3? with GSK-3?RNAiLV increased the cell proliferation, whereas overexpression of GSK-3? with GC-GSK-3?LV decreased the proliferation. Both SB216763 and GSK-3?RNAiLV significantly increased the levels of ?-catenin and cyclin D1 in the cells, whereas GSK-3? overexpression decreased their levels. In rats with a partial hepatectomy, administration of SB216763 (2 mg/kg, ip) significantly increased the number of oval cells, the levels of phospho-Ser9-GSK-3?, ?-catenin and cyclin D1 in liver, as well as the ratio of liver weight to femur length at d 7 after the surgery.GSK-3? suppresses the proliferation of hepatic oval cells by modulating the Wnt/?-catenin signaling pathway.

SUBMITTER: Ji XK 

PROVIDER: S-EPMC4349928 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature