title: GSK-3β suppresses the proliferation of rat hepatic oval cells through modulating Wnt/β-catenin signaling pathway.
abstract: OBJECTIVE
  Glycogen synthase kinase 3β (GSK-3β) plays a crucial role in hepatic biology, including liver development, regeneration, proliferation and carcinogenesis. In this study we investigated the role of GSK-3β in regulation of growth of hepatic oval cells in vitro and in liver regeneration in partially hepatectomized rats.
  
  
  METHODS
  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-3β (GSK-3βRNAiLV) or a lentivirus that overexpressed GSK-3β (GC-GSK-3βLV). Adult rats underwent partial (70%) hepatectomy, and liver weight and femur length were measured at d 7 after the surgery. The expression of GSK-3β, phospho-Ser9-GSK-3β, β-catenin and cyclin D1 was examined with immunoblotting assays or immunohistochemistry.
  
  
  RESULTS
  Treatment of WB-F344 cells with the GSK-3β inhibitor SB216763 (5 and 10 μmol/L) dose-dependently increased the levels of phospho-Ser9-GSK-3β, but not the levels of total GSK-3β, and promoted the cell proliferation. Knockout of GSK-3β with GSK-3βRNAiLV increased the cell proliferation, whereas overexpression of GSK-3β with GC-GSK-3βLV decreased the proliferation. Both SB216763 and GSK-3βRNAiLV significantly increased the levels of β-catenin and cyclin D1 in the cells, whereas GSK-3β 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-3β, β-catenin and cyclin D1 in liver, as well as the ratio of liver weight to femur length at d 7 after the surgery.
  
  
  CONCLUSIONS
  GSK-3β suppresses the proliferation of hepatic oval cells by modulating the Wnt/β-catenin signaling pathway.
authors: Department of General Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors: Xiao-ke
authors: XK
authors: Ji
authors: Department of General Surgery, the First Affiliated Hospital of Gannan Medical College, Ganzhou 341000, China.
authors: Yuan-kang
authors: YK
authors: Xie
authors: Department of General Surgery, Ganzhou People's Hospital, Ganzhou 341000, China.
authors: Jun-qiao
authors: JQ
authors: Zhong
authors: Department of General Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors: Qi-gang
authors: QG
authors: Xu
authors: Department of General Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors: Qi-qiang
authors: QQ
authors: Zeng
authors: Department of General Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors: Yang
authors: Y
authors: Wang
authors: Department of General Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors: Qi-yu
authors: QY
authors: Zhang
authors: Department of General Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors: Yun-feng
authors: YF
authors: Shan
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D057809:HEK293 Cells; D006498:Hepatectomy; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D009929:Organ Size; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C530106:Ccnd1 protein, rat; C495268:Ctnnb1 protein, rat; D047428:Protein Kinase Inhibitors; D051176:beta Catenin; D019938:Cyclin D1; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3