start-ver=1.4 cd-journal=joma no-vol=46 cd-vols= no-issue=1 article-no= start-page=119 end-page=126 dt-received= dt-revised= dt-accepted= dt-pub-year=2009 dt-pub=200904 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Induction of hepatocyte growth factor production in human dermal fibroblasts and their proliferation by the extract of bitter melon pulp en-subtitle= kn-subtitle= en-abstract= kn-abstract=Hepatocyte growth factor (HGF) is useful as a potential therapeutic agent for hepatic and renal fibrosis and cardiovascular diseases through inducing proliferation of epithelial and endothelial cells. HGF inducers may also be useful as therapeutic agents for these diseases. However, there have been no reports on induction of HGF production by plant extracts or juices. An extract of bitter melon (Momordica charantia L.) pulp markedly induced HGF production. There was a time lag of 72 h before induction of HGF production after the extract addition. Its stimulatory effect was accompanied by upregulation of HGF gene expression. Increases in mitogen-activated protein kinases (MAPKs) were observed from 72 h after the extract addition. Inhibitors of MAPKs suppressed the extract-induced HGF production. The extract also stimulated cell proliferation. Both activities for induction of HGF production and cell proliferation were eluted together in a single peak with 14,000 Da on gel filtration. The results indicate that bitter melon pulp extract induced HGF production and cell proliferation of human dermal fibroblasts and suggest that activation of MAPKs is involved in the HGF induction. Our findings suggest potential usefulness of the extract for tissue regeneration and provide an insight into the molecular mechanism underlying the wound-healing property of bitter melon. en-copyright= kn-copyright= en-aut-name=OnoTakehiro en-aut-sei=Ono en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujiTomoe en-aut-sei=Tsuji en-aut-mei=Tomoe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SakaiMiho en-aut-sei=Sakai en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YukizakiChizuko en-aut-sei=Yukizaki en-aut-mei=Chizuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=InoHisatoshi en-aut-sei=Ino en-aut-mei=Hisatoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AkagiIsao en-aut-sei=Akagi en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HiramatsuKaori en-aut-sei=Hiramatsu en-aut-mei=Kaori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MatsumotoYohsuke en-aut-sei=Matsumoto en-aut-mei=Yohsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SugiuraYoshihiro en-aut-sei=Sugiura en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=UtoHirofumi en-aut-sei=Uto en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TsubouchiHirohito en-aut-sei=Tsubouchi en-aut-mei=Hirohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=GohdaEiichi en-aut-sei=Gohda en-aut-mei=Eiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil= kn-affil=Department of Immunochemistry, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Immunochemistry, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Miyazaki Prefectural Food R&D Center affil-num=4 en-affil= kn-affil=Miyazaki Prefectural Food R&D Center affil-num=5 en-affil= kn-affil=Miyazaki Agricultural Research Institute affil-num=6 en-affil= kn-affil=Miyazaki Prefectural Industrial Support Foundation affil-num=7 en-affil= kn-affil=Department of Immunochemistry, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=8 en-affil= kn-affil=Department of Immunochemistry, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=9 en-affil= kn-affil=Department of Immunochemistry, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=10 en-affil= kn-affil=Department of Digestive Disease and Life-style Related Diseases, Health Research Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences affil-num=11 en-affil= kn-affil=Department of Digestive Disease and Life-style Related Diseases, Health Research Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences affil-num=12 en-affil= kn-affil=Department of Immunochemistry, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences en-keyword=Hepatocyte growth factor kn-keyword=Hepatocyte growth factor en-keyword=Bitter melon kn-keyword=Bitter melon en-keyword=Extracellular signal-regulated kinase kn-keyword=Extracellular signal-regulated kinase en-keyword=Cell proliferation kn-keyword=Cell proliferation en-keyword=Dermal fibroblast kn-keyword=Dermal fibroblast END