| Project/Area Number |
11670477
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Universtiy of Tokyo |
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Principal Investigator |
YASUDA Hiroshi Univ. of Tokyo School of Medicine, Assit. Prof., 医学部・附属病院・分院, 助手 (80262129)
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| Co-Investigator(Kenkyū-buntansha) |
OHNISHI Hiroshide Univ. of Tokyo School of Medicine, Assit. Prof., 医学部・附属病院・分院, 助手 (00313023)
MINE Tetsuya University of Tokyo School of Medicine, Associate Prof., 医学部・附属病院・分院, 講師 (20157572)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | liver regeneration / Smad / activin / TGF-β / 肝再生抑制因子 |
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| Research Abstract |
Transforming growth factor (TGF)-β and activin A inhibit the growth and induce cell death of parenchymal liver cells. Smad proteins have recently been identified as intracellular signaling mediators and modulators of TGF-β family members. This study assessed the role of Smad proteins during the action of TGF-β and activin A on liver cells using a well-differentiated hepatoma cell line, Hep3B cells. To study the role of Smad proteins in the apoptosis-inducing, anti-proliferative activities of TGF-β and activin A in liver cells, we stably transfected dominant negative Smad2-3SA or Smad3-3SA mutants in Hep3B cells. Transfection of Smad2-3SA or Smad3-3SA abrogated both TGF-β-induced and activin A-induced apoptosis and growth inhibition of Hep3B cells. We also demonstrate that transfection of Smad7, an intracellular antagonist of Smad signaling, inhibited both TGF-β- and activin A-induced apoptosis and growth inhibition of these cells. These results suggest that Smad proteins positively and negatively mediate TGF-β-induced and activin A-induced apoptosis and growth inhibition of liver cells.
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