Inhibitory Effects of Dexamethasone on Hepatocyte Growth Factor-Induced DNA Synthesis and Proliferation in Primary Cultures of Adult Rat Hepatocytes
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We investigated the effects of dexamethasone on hepatocyte growth factor (HGF)-induced DNA synthesis and proliferation in serum-free primary cultures of adult rat hepatocytes. Isolated hepatocytes were cultured at a density of 3.3 × 104 cells/cm2 in Williams' medium E containing 5% newborn bovine serum and various concentrations of dexamethasone for 1, 2, and 3 h. After a 3-h attachment period, the medium was then changed, and cells were cultured in serum-free, and dexamethasone (10-10 M)-contained Williams' medium E with or without glucocorticoid receptor antagonists. After addition of dexamethasone to the culture medium, the growth-stimulating effects of HGF (5 ng/mL) on the primary cultured hepatocytes were time- and dose-dependently inhibited. The mineralcorticoid aldosterone (10-7 M) did not produce the same growth-inhibitory effects as dexamethasone (10-8 M). The inhibitory effects of dexamethasone were reversed by treatment with the glucocorticoid receptor antagonist mifepristone (RU486, 10-6 M) or a monoclonal antibody against glucocorticoid receptor (100 ng/mL). In addition, the growth-inhibitory dose of dexamethasone did not affect HGF-inducedreceptor tyrosine kinase and extracellular signal-regulated kinase 2 phosphorylation. These results indicate that dexamethasone dose-dependently delays and inhibits HGF-induced DNA synthesis and proliferation through its own intracellular receptor in primary cultures of adult rat hepatocytes.Ｆｕｌｌ Paper. 出版社版はJ-Stageで公開
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