EVL is a novel focal adhesion protein involved in the regulation of cytoskeletal dynamics and vascular permeability.

EVL is a novel focal adhesion protein involved in the regulation of cytoskeletal dynamics and vascular permeability.
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DOI:
10.1177/20458940211049002
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发表时间:
2021-10
影响因子:
2.6
通讯作者:
Garcia JGN
Garcia JGN
中科院分区:
医学4区
文献类型:
--
作者:
Mascarenhas JB;Gaber AA;Larrinaga TM;Mayfield R;Novak S;Camp SM;Gregorio C;Jacobson JR;Cress AE;Dudek SM;Garcia JGN

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肺血管通透性增加是炎症性疾病的一个主要特征,它代表了血管收缩力和屏障恢复力的不平衡,这两种力都高度依赖于肌动蛋白细胞骨架。目前的研究探讨了Ena-VASP样蛋白(EVL)在调节血管通透性反应和肺内皮细胞屏障完整性中的作用,EVL是Ena-VASP家族的一员,已知可调节肌动蛋白细胞骨架。利用跨内皮电阻(TEER)的变化来测量内皮细胞的屏障反应,我们证明EVL的表达调节内皮细胞对血管屏障增强激动剂鞘氨醇-1-磷酸(S1P)和凝血酶(一种屏障破坏刺激物)的反应。全内反射荧光表明,EVL存在于内皮细胞的局灶黏附中,并影响局灶黏附的大小、分布和因S1P和凝血酶的刺激而产生的局灶黏附的数量,其中局灶黏附激酶(FAK)是S1P刺激的EVL转导内皮细胞的关键因素,但在凝血酶诱导的局灶黏附重排中作用有限。总之,这些数据表明EVL是一种局灶黏附蛋白,密切参与调节内皮细胞屏障改变刺激的细胞骨架反应。关键词:细胞骨架,血管屏障,鞘氨醇-1-磷酸,凝血酶,黏附激酶(FAK), Ena-VASP样蛋白(EVL),细胞骨架调节蛋白
Increases in lung vascular permeability is a cardinal feature of inflammatory disease and represents an imbalance in vascular contractile forces and barrier-restorative forces, with both forces highly dependent upon the actin cytoskeleton. The current study investigates the role of Ena-VASP-like (EVL), a member of the Ena-VASP family known to regulate the actin cytoskeleton, in regulating vascular permeability responses and lung endothelial cell barrier integrity. Utilizing changes in transendothelial electricial resistance (TEER) to measure endothelial cell barrier responses, we demonstrate that EVL expression regulates endothelial cell responses to both sphingosine-1-phospate (S1P), a vascular barrier-enhancing agonist, and to thrombin, a barrier-disrupting stimulus. Total internal reflection fluorescence demonstrates that EVL is present in endothelial cell focal adhesions and impacts focal adhesion size, distribution, and the number of focal adhesions generated in response to S1P and thrombin challenge, with the focal adhesion kinase (FAK) a key contributor in S1P-stimulated EVL-transduced endothelial cell but a limited role in thrombin-induced focal adhesion rearrangements. In summary, these data indicate that EVL is a focal adhesion protein intimately involved in regulation of cytoskeletal responses to endothelial cell barrier-altering stimuli. Keywords: cytoskeleton, vascular barrier, sphingosine-1-phosphate, thrombin, focal adhesion kinase (FAK), Ena-VASP like protein (EVL), cytoskeletal regulatory protein
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