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

TGF-β/激活素信号通路在肝再生中的作用。

• 批准号: 11670477
• 负责人: YASUDA Hiroshi
• 金额: $ 1.41万
• 依托单位: Universtiy of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670477/
• 关键词: liver regeneration; Smad; activin; TGF-β; 肝再生抑制因子

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.

转化生长因子 (TGF)-β 和激活素 A 抑制实质肝细胞的生长并诱导细胞死亡。 Smad 蛋白最近被鉴定为 TGF-β 家族成员的细胞内信号传导介质和调节剂。本研究使用分化良好的肝癌细胞系 Hep3B 细胞评估了 Smad 蛋白在 TGF-β 和激活素 A 对肝细胞作用过程中的作用。为了研究 Smad 蛋白在肝细胞中 TGF-β 和激活素 A 的凋亡诱导、抗增殖活性中的作用，我们在 Hep3B 细胞中稳定转染显性失活 Smad2-3SA 或 Smad3-3SA 突变体。 Smad2-3SA 或 Smad3-3SA 的转染消除了 TGF-β 诱导和激活素 A 诱导的 Hep3B 细胞凋亡和生长抑制。我们还证明，Smad7（一种 Smad 信号传导的细胞内拮抗剂）的转染可抑制 TGF-β 和激活素 A 诱导的细胞凋亡和生长抑制。这些结果表明，Smad 蛋白正向和负向介导 TGF-β 诱导和激活素 A 诱导的肝细胞凋亡和生长抑制。

项目成果

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)

Ueda N、Ohnishi H、Kanamaru C、Suzuki J、Tsuchida T、Mashima H、Yasuda H、Fujita T.：“驱动蛋白参与大鼠胰淀粉酶分泌的调节。”胃肠病学。

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.Cl

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 参与幽门螺杆菌空泡细胞毒素诱导的空泡形成

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.. 1

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 参与幽门螺杆菌空泡细胞毒素诱导的空泡形成

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)

Ueda N，Ohnishi H，Kanamaru C，Suzuki J，Tsuchida T，Mashima H，Yasuda H，Fujita T.：“驱动蛋白参与大鼠胰淀粉酶分泌的调节。”胃肠病学。

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)

Chang-Seon Myung、Hiroshi Yasuda、Wendy W Liu 等人：“类异戊二烯脂质在决定效应子激活中对异三聚体 G 蛋白 γ 亚基的作用”《生物化学杂志》第 274 卷第 23 期（1999 年）。