通过稳定拉伸和脉动性对血管焦点粘附激酶的差调节
Stéphanie Lehoux1, Bruno Esposito, Régine Merval
1INSERM U541, Hôpital Lariboisière, 41, Boulevard de la Chapelle, 75010 Paris, France. lehoux@larib.inserm.fr
稳定的动脉拉伸激活焦粘附激酶 (FAK),涉及Src和整合素,而脉动式拉伸并没有显著地激活FAK. 这突出了动脉中差异性的机械信号传导.
科学领域:
- 血管生物学 血管生物学
- 机械转导是指机械转导的过程.
- 细胞信号传递 细胞信号传递
背景情况:
- 动脉张力应变具有稳定和脉动的组成部分.
- 在整个血管中,这些机械刺激的差异转导并未得到充分理解.
研究的目的:
- 研究稳定和脉动拉伸对血管信号通路的差异效应.
- 阐明焦粘附激酶 (FAK) 和其上游调节者的作用,以应对动脉中的机械应力.
主要方法:
- 在器官培养中保持了子的大动脉.
- 使用高内压力 (150 mm Hg) 来模拟稳定的拉伸.
- 应用循环拉伸 (10%) 来模拟脉动式拉伸.
- 评估了焦点粘附激酶 (FAK) 酸化和细胞外调节激酶 (ERK) 1/2的激活.
- 使用了Src家族激酶 (PP2) 和整体蛋白-细胞外基质相互作用 (RGD) 的抑制剂.
主要成果:
- 在大动脉组织中,高的内压力显著增加了FAK酸化在多重氨酸残留物 (Tyr-397,Tyr-407,Tyr-861,Tyr-925) 中.
- 稳压FAK激活被PP2和RGD降低,涉及Src和整合素.
- PP2和RGD抑制了FAK与Grb2的结合,并在稳压下阻止了ERK1/2的激活.
- 循环拉伸没有诱导显著的FAK酸化.
- 循环拉伸激活了ERK1/2,但这种激活不受PP2或RGD的影响.
结论:
- 稳定和循环拉伸在主动脉中以不同的方式转化.
- 稳定压力诱导的FAK激活涉及Src和整合素.
- 脉冲拉伸似乎不涉及FAK在其信号通路中.
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