Inhibition of Hepatocyte Growth Factor Production in Human Fibroblasts by Ursodeoxycholic Acid(Pharmacology)
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概要
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Hepatocyte growth factor (HGF) stimulates the proliferation of hepatocytes and biliary epithelial cells and protects hepatocytes from apoptosis induced by various stimuli. In view of HGF induction by interferons, substances used for the treatment of chronic hepatitis C, this study was conducted to determine whether ursodeoxycholic acid (UDCA), which is widely used for the treatment of cholestatic liver diseases, modulates HGF production. UDCA did not induce HGF production in human dermal fibroblasts, but it potently inhibited phorbol-12-myristate-13-acetate (PMA)- and cholera-toxin-induced HGF production without affecting cell viability. The inhibitory effects of UDCA were as potent as those of transforming growth factor-β1 and dexamethasone. Up-regulations of HGF gene expression induced by PMA and cholera toxin were also inhibited by UDCA. Moreover, UDCA dose-dependently inhibited high constitutive HGF production by MRC-5 cells without decreasing cell viability. Deoxycholate, chenodeoxycholate, taurochenodeoxycholate and glycochenodeoxycholate also inhibited cholera-toxin-induced HGF production at non-cytotoxic doses. UDCA, however, had no apparent effect on PMA-induced phosphorylation of mitogen-activated protein kinase, which is crucial for HGF induction by PMA. These results indicate that non-cytotoxic doses of UDCA inhibited constitutive and induced HGF production and suggest that UDCA supplemented with HGF or HGF inducers could have a more potential therapeutic effect.
- 公益社団法人日本薬学会の論文
- 2005-04-01
著者
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Tsubouchi Hirohito
Department of Digestive and Lifestyle-related Diseases, Human Environmental Sciences, Health Researc
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MIYAZAKI Masahiro
Department of Cell Biology, Okayama University Graduate School of Medicine and Dentistry
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Yamamoto Itaru
岡山大学 薬学部免疫医薬品化学
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YAMAMOTO Itaru
Department of Radiology, Kanazawa Medical University
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GOHDA Eiichi
Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University
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HIRAMATSU Kaori
Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University
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MATSUMOTO Yohsuke
Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University
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Yamamoto Itaru
Department Of Immunochemistry Faculty Of Pharmaceutical Science Okayama University
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Gohda Eiichi
Dep. Of Immunochemistry Div. Of Pharmaceutical Sciences Okayama Univ. Graduate School Of Medicine De
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Gohda E
Department Of Immunochemistry Faculty Of Pharmaceutical Sciences Okayama University
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Gohda Eiichi
Department Of Immunochemistry Division Of Pharmaceutical Sciences Okayama University Graduate School
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Tsubouchi Hirohito
Department Of Digestive And Life-style Related Disease Health Research Course Human And Environmenta
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Miyazaki Masahiro
Department Of Cell Biology Okayama University Graduate School Of Medicine And Dentistry
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Miyazaki Masahiro
Department Of Cell Biology Institute Of Cellular And Molecular Biology Okayama University Medical Sc
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Hiramatsu Kaori
Department Of Immunochemistry Faculty Of Pharmaceutical Sciences Okayama University
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Matsumoto Yohsuke
Department Of Immunochemistry Faculty Of Pharmaceutical Sciences Okayama University
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GOHDA Eiichi
Department of Biochemistry, Faculty of Dentistry, Osaka University
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