Role of TGF-β/activin signaling pathway in liver regeneration.

• Project/Area Number: 11670477
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Universtiy of Tokyo
• Principal Investigator: YASUDA Hiroshi Univ. of Tokyo School of Medicine, Assit. Prof., 医学部・附属病院・分院, 助手 (80262129)
• 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)
• Project Period (FY): 1999 – 2000
• Project Status: Completed (Fiscal Year 2000)
• Budget Amount: ¥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)
• Keywords: liver regeneration / Smad / activin / TGF-β / 肝再生抑制因子

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.

Research Products

• [Publications] Myung CS,Yasuda H,Liu WW,Harden TK,Garrison JC.: "Role of isoprenoid lipid on the heterotrimeric G protein γ subunit in determining effector activation."J.Biol.Chem.. 274. 16595-16603 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ueda N,Ohnishi H,Kanamaru C,Suzuki J,Tsuchida T,Mashima H,Yasuda H,Fujita T.: "Kinesin is involved in the regulation of rat pancreatic amylase secretion."Gastroenterology. 119. 1123-1131 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Suzuki J,Ohnishi H,Shibata H,Wada A,Hirayama T,Iiri T,Ueda N,Kanamaru C,Tsuchida T,Mashima H,Yasuda H,Fujita T.: "Dynamin is involved in the vacuolation induced by Helicobacter pylori vacuolating cytotoxin (VacA) in human epithelial cells."J.Clin.Invest.. 107. 363-370 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Myung CS, Yasuda H, Liu WW, Harden TK, Garrison JC.: "Role of isoprenoid lipid on the heterotrimeric G protein γ subunit in determining effector activation."J.Biol.Chem.. 274. 16595-16603 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ueda N, Ohnishi H, Kanamaru C, Suzuki J, Tsuchida T, Mashima H, Yasuda H, Fujita T.: "Kinesin is involved in the regulation of rat pancreatic amylase secretion."Gastroenterology. 119. 1123-1131 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Suzuki J, Ohnishi H, Shibata H, Wada A, Hirayama T, Iiri T, Ueda N, Kanamaru C, Tsuchida T, Mashima H, Yasuda H, Fujita T.: "Dynamin is involved in the vacuolation induced by Helicobacter pylori vacuolating cytotoxin (VacA) in human epithelial cells."J.Clin.Invest.. 107. 363-370 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Myung CS,Yasuda H,Liu WW,Harden TK,Gamison JC.: "Role of isoprenoid lipid on the heterotrimeric G protein γ subunit in determining effector activation."J.Biol.Chem.. 274. 16595-16603 (1999)
• [Publications] Ueda N,Ohnishi H,Kanamaru C,Suzuki J,Tsuchida T,Mashima H,Yasuda H,Fujita T.: "Kinesin is involved in the regulation of rat pancreatic amylase secretion."Gastroenterology. 119. 1123-1131 (2000)
• [Publications] Suzuki J,Ohnishi H,Shibata H,Wada A,Hirayama T,lin T,Ueda N,Kanamaru C,Tsuchida T,Mashima H,Yasuda H,Fujita T.: "Dynamin is involved in the vacuolation induced by Helicobacter pylon vacuolating cytotoxin (VacA) in human epithelial cells."J.Clin.Invest.. 107. 363-370 (2001)
• [Publications] Chang-Seon Myung, Hiroshi Yasuda, Wendy W Liu, et al.: "Role of isoprenoid lipids on the heterotrimeric G protein γ subunit in determining effector acfivation"Journal of Biological Chemistry. Vol274 No23. 16595-16603 (1999)