Effects of transforming growth factor-betas on endothelial anticoagulant activity

转化生长因子-β对内皮抗凝活性的影响

• 批准号: 05807070
• 负责人: KARASAKI Yuji
• 金额: $ 1.15万
• 依托单位: Univ.of Occ.& Env.Health, Sch of Med.
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05807070/
• 关键词: Thrombomodulin; Human Umbilical Vein Endothelial Cells; Transforming Growth Factor Beta; thrombogenesis; トロンボモデュリン; 動脈硬化; トロンボモジュリン

To investigate the effects of transforming growth factor-betas (TGF-betas) on endothelial anticoagulant activity, we assayd thrombomodulin (TM) activity and antigen levels of human umbilical vein endothelial cells (HUVECs) incubated with TGF-betas in vitro. TGF-beta1 suppressed surface TM activity and surface TM antigen levels maximally 12 h after incubation by dose-dependent manners. TGF-beta2 was almost equipotent with TGF-beta1 for the suppression of them. Both TGF-betas suppressed total TM antigen level in HUVECs, and the time course of the suppression was similar to that of the cell surface TM antigen level. The maximal reductions of TM mRNA levels by TGF-betas were observed at several hours ahead of those observed in both surface and total TM antigen levels, suggesting that the TGF-beta-mediated suppression of TM antigen of HUVECs is primarily regulated at the TM mRNA level. Our present work suggests that the down-modulation of TM level induced by TGF-betas in HUVECs contributes in vivo to promoting the thrombogenesis either at the sites of injury of vessel walls, such as atherosclerotic lesions where TGF-beta1 is released from platelets, smooth muscle cells and monocytes, or at neovascular walls in tumors secreting TGF-beta2.

为了研究转化生长因子β（transforminggrowthfactor-betas，TGF-betas）对内皮细胞抗凝活性的影响，我们检测了体外培养的人脐静脉内皮细胞（humanumbilicalveinendothelialcells，HUVECs）的血栓调节蛋白（thrombomodulin，TM）活性和抗原水平。TGF-β 1抑制表面TM活性和表面TM抗原水平最大12小时后孵育剂量依赖性的方式。TGF-β 2与TGF-β 1对它们的抑制作用几乎相等。两种TGF-β抑制HUVEC中的总TM抗原水平，并且抑制的时间过程与细胞表面TM抗原水平的时间过程相似。TGF-β对TM mRNA水平的最大降低比在表面和总TM抗原水平中观察到的那些提前几个小时观察到，这表明TGF-β介导的对HUVEC的TM抗原的抑制主要在TM mRNA水平调节。我们目前的工作表明，在HUVEC中由TGF-β诱导的TM水平的下调有助于在体内促进血管壁损伤部位的血栓形成，例如动脉粥样硬化病变，其中TGF-β 1从血小板、平滑肌细胞和单核细胞释放，或者在分泌TGF-β 2的肿瘤中的新生血管壁。

项目成果

Taro Ohji: "Transforming Growth Factor Betal and Beta2 Induce Down-Modulation of Thrombomodulin in Human Umbilical Vein Endothelial Cells" Thrombosis and Haemostasis. 73 (5). 1995

Taro Ohji：“转化生长因子 Beta 和 Beta2 诱导人脐静脉内皮细胞中血栓调节蛋白的下调”血栓形成和止血。

TARO OHJI: "Transforming Growth Factor Betal and Beta2 Induce Down-Modulation of Thrombomodulin in Human Umbilical Vein Endothelial Cells" Thrombosis and Haemostasis. 73(5). (1995)

TARO OHJI：“转化生长因子 β1 和 β2 诱导人脐静脉内皮细胞中血栓调节蛋白的下调”血栓形成和止血。

TARO OHJI: "Transforming Growth Factor Betal and Beta2 Induce Down-Modulation of Thrombomodulin in Human Umbilical Vein Endothelial Cells" Thrombosis and Haemostasis. in Press.

TARO OHJI：“转化生长因子 β1 和 β2 诱导人脐静脉内皮细胞中血栓调节蛋白的下调”血栓形成和止血。