Inhibitory Effects of Dexamethasone on Hepatocyte Growth Factor-Induced DNA Synthesis and Proliferation in Primary Cultures of Adult Rat Hepatocytes
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- Kimura Mitsutoshi
- Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Josai University, Japan
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- Moteki Hajime
- Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Josai University, Japan
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- Ogihara Masahiko
- Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Josai University, Japan
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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 dexamethasone (10−10 M)-containing 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-induced receptor 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.
収録刊行物
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 115 (3), 390-398, 2011
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390282680154770688
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- NII論文ID
- 10029892847
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- NII書誌ID
- AA11806667
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- ISSN
- 13478648
- 13478613
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- NDL書誌ID
- 11010057
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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