Endothelial FAK as a therapeutic target in disease.
Endothelial FAK as a therapeutic target in disease.
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DOI：
10.1016/j.mvr.2011.09.011
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发表时间：
2012-01
影响因子：
3.1
通讯作者：
Jacobson JR
中科院分区：
文献类型：
--
作者：
Infusino GA;Jacobson JR
粘着斑（FA）是内皮细胞骨架通过跨膜受体、整合素和整合素相关的细胞内蛋白与细胞外基质（ECM）相互作用的重要介质。这种通讯对于包括EC屏障调节在内的多种细胞过程是必不可少的，并且由非受体蛋白酪氨酸激酶、粘着斑激酶（FAK）介导。由于FA介导EC对各种刺激的基本反应，并且FAK对于这些反应是必不可少的，因此靶向EC FAK作为各种疾病的治疗策略的想法是非常有希望的。特别是，FAK的抑制可以通过对EC增殖和血管生成的影响证明在多种癌症中是有益的，通过减弱肺血管通透性在急性肺损伤（ALI）中是有益的，并且通过减少滑膜血管生成在类风湿性关节炎中是有益的。此外，FAK抑制剂在心血管疾病和糖尿病肾病中也有潜在的治疗益处。目前存在几种靶向EC FAK的药物，包括目前正在临床前模型中研究的药物以及容易获得的药物，如鞘脂类似物FTY 720和他汀类药物。随着EC FAK在各种疾病发病机制中的作用不断被探索和新的见解被揭示，FAK的药物靶向将继续成为一个重要的研究领域，并可能最终导致高度新颖和有效的策略来治疗这些疾病。
Focal adhesions (FA) are important mediators of endothelial cytoskeletal interactions with the extracellular matrix (ECM) via transmembrane receptors, integrins and integrin-associated intracellular proteins. This communication is essential for a variety of cell processes including EC barrier regulation and is mediated by the non-receptor protein tyrosine kinase, focal adhesion kinase (FAK). As FA mediate the basic response of EC to a variety of stimuli and FAK is essential to these responses, the idea of targeting EC FAK as a therapeutic strategy for an assortment of diseases is highly promising. In particular, inhibition of FAK could prove beneficial in a variety of cancers via effects on EC proliferation and angiogensis, in acute lung injury (ALI) via the attenuation of lung vascular permeability, and in rheumatoid arthritis via reductions in synovial angiogensis. In addition, there are potential therapeutic benefits of FAK inhibition in cardiovascular disease and diabetic nephropathy as well. Several drugs that target EC FAK are now in existence and include agents currently under investigation in preclinical models as well as drugs that are readily available such as the sphingolipid analog FTY720 and statins. As the role of EC FAK in the pathogenesis of a variety of diseases continues to be explored and new insights are revealed, drug targeting of FAK will continue to be an important are of investigation and may ultimately lead to highly novel and effective strategies to treat these diseases.
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影响因子：
--
作者：
JOHNSON, BA;HAINES, GK;KOCH, AE
通讯作者：
KOCH, AE
影响因子：
4.8
作者：
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影响因子：
5.4
作者：
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通讯作者：
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影响因子：
56.9
作者：
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通讯作者：
CHERESH, DA
DOI：
10.1165/rcmb.2003-0267oc
发表时间：
2004-05-01
影响因子：
6.4
作者：
Jacobson, JR;Dudek, SM;Garcia, JGN
通讯作者：
Garcia, JGN