2009 Fiscal Year Final Research Report
A role of hepatocyte growth factor in regulation of hepatic development and differentiation
| Project/Area Number |
19209028
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Kagoshima University |
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Principal Investigator |
TSUBOUCHI Hirohito Kagoshima University, 大学院・医歯学総合研究科, 教授 (60145480)
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| Co-Investigator(Kenkyū-buntansha) |
IDO Akio 鹿児島大学, 大学院・医歯学総合研究科, 准教授 (30291545)
OKETANI Makoto 鹿児島大学, 医学部・歯学部附属病院, 講師 (50274816)
UTO Hirofumi 鹿児島大学, 大学院・医歯学総合研究科, 講師 (20347058)
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| Project Period (FY) |
2007 – 2009
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| Keywords | 肝臓病学 |
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| Research Abstract |
Induction of hepatic differentiation of iPS cells requires multiple steps including induction of endodermal, hepatic endodermal, and hepatic progenitor cells, and maturation of hepatocytes. In this study, we found that, HGF increased albumin and alpha-fetoprotein expression in hepatic endodermal cells, which were induced in embryoid bodies of iPS cells treated with Activin A, bFGF, followed by BMP-2 and FGF-4 exposure. These results indicate that HGF plays an essential role in hepatic differentiation of hepatic endodermal cells. Conversely, hepatic endodermal cells expressed Dlk1, but not EpCAM, meaning the possibility that hepatoblast-like cells exist in the hepatic endodermal cells. The findings in this study contribute to establishment of novel cell transplantation therapies for intractable liver diseases using HGF-induced high efficient hepatic differentiation. Conversely, HGF is also essential for repair and regeneration of various injured tissues. Actually, HGF stimulated migration of gastric epithelial cells through modification of tight junction proteins, resulting in increased epithelial restitution in an in vitro ulcer model. Additionally, administration of HGF decreased pulmonary arterial pressure in a rat model of pulmonary arterial hypertension, resulting in prolonged animal survival. These results also indicate that HGF itself is a potent therapeutic agent for various intractable diseases.
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[Presentation] A fragment of high molecular weight kininogen is upregulated in patients with non-alcoholic fatty liver diserse2008
Author(s)
Uto H, Sato Y, Tanoue S, Ishida Y, Tamai T, Hasegawa S, Oketani M, Ido A, Nakajima T, Okanoue T, Tsubouchi H
Organizer
59th Annual Meeting of American Association for the Study of Live Diseas
Place of Presentation
San Francisco
Year and Date
20081031-20081104
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[Presentation] Trasnlational research of HGF: A phaseI/IIstudy of recombinant human HGF for the treatment of fulminant hepatic failure2007
Author(s)
Ido A, Moriuchi A, Marusawa H, Ikeda K, Numata M, Yamaji N, Setoyama H, Ida H, Oketani M, Chiba T, Tsubouchi H
Organizer
6th JSH Single Topic Conferens "Liver Failure:Recent Progress from Pathogenesis to Management"
Place of Presentation
安比市
Year and Date
20070928-20070929
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[Presentation] Proteomic analysis of serum biomarkers in patients with nonalcoholic steatohepatitis using SEDI-TOF/MS or MALDI-TOF/MS2007
Author(s)
Uto H, Sato Y, Ishida Y, Takami Y, Kanmura S, Moriuchi A, Hasegawa S, Oketani M, Ido A, Nakajima T, Okanoue T, Tsubouchi H
Organizer
The 58th Annual Meeting of the American Association for the Study of the Live Disease
Place of Presentation
Boston
Year and Date
20070902-20070906
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