| 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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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥49,920,000 (Direct Cost: ¥38,400,000、Indirect Cost: ¥11,520,000)
Fiscal Year 2009: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
Fiscal Year 2008: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2007: ¥25,610,000 (Direct Cost: ¥19,700,000、Indirect Cost: ¥5,910,000)
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| Keywords | 肝臓病学 / 肝細胞増殖因子(HGF) / iPS細胞 / 肝細胞分化 / 上皮間葉転換 / 細胞移植 / tight juction protein / 細胞遊走 / epithelial restitution / 肺高血圧症 / 肝星細胞 / 腎メサンギウム細胞 / 臓器線維化 |
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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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