A functional siRNA screen identifies RhoGTPase-associated genes involved in thrombin-induced endothelial permeability.
A functional siRNA screen identifies RhoGTPase-associated genes involved in thrombin-induced endothelial permeability.
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DOI：
10.1371/journal.pone.0201231
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Hordijk PL
中科院分区：
文献类型：
--
作者：
Amado-Azevedo J;de Menezes RX;van Nieuw Amerongen GP;van Hinsbergh VWM;Hordijk PL
凝血酶和其他炎症介质可能通过破坏相邻内皮细胞之间的粘附连接来诱导血管通透性。如果不加以控制，渗透性过高会导致屏障受损、液体渗漏和水肿，从而导致多器官衰竭和死亡。 RhoGTPases 控制细胞骨架动力学、粘附和迁移，并且是已知的内皮完整性调节剂。关于每种 RhoGTPase 及其相关调节基因和效应基因在内皮完整性中的精确作用的知识尚不完整。将 RNAi 筛选与电阻抗测量相结合，我们量化了单独沉默 270 个 Rho 相关基因对凝血酶激活的原代内皮细胞屏障功能的影响。确定了调节凝血酶反应的已知和新型 RhoGTPase 相关调节因子（RTKN、TIAM2、MLC1、ARPC1B、SEPT2、SLC9A3R1、RACGAP1、RAPGEF2、RHOD、PREX1、ARHGEF7、PLXNB2、ARHGAP45、SRGAP2、ARHGEF5）。总之，通过这种 siRNA 筛选，我们证实了已知的内皮完整性调节因子的作用，同时也确定了凝血酶诱导的内皮信号传导中新的、潜在的关键参与者。
Thrombin and other inflammatory mediators may induce vascular permeability through the disruption of adherens junctions between adjacent endothelial cells. If uncontrolled, hyperpermeability leads to an impaired barrier, fluid leakage and edema, which can contribute to multi-organ failure and death. RhoGTPases control cytoskeletal dynamics, adhesion and migration and are known regulators of endothelial integrity. Knowledge of the precise role of each RhoGTPase, and their associated regulatory and effector genes, in endothelial integrity is incomplete. Using a combination of a RNAi screen with electrical impedance measurements, we quantified the effect of individually silencing 270 Rho-associated genes on the barrier function of thrombin-activated, primary endothelial cells. Known and novel RhoGTPase-associated regulators that modulate the response to thrombin were identified (RTKN, TIAM2, MLC1, ARPC1B, SEPT2, SLC9A3R1, RACGAP1, RAPGEF2, RHOD, PREX1, ARHGEF7, PLXNB2, ARHGAP45, SRGAP2, ARHGEF5). In conclusion, with this siRNA screen, we confirmed the roles of known regulators of endothelial integrity but also identified new, potential key players in thrombin-induced endothelial signaling.
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影响因子：
11.8
作者：
Durkin CH;Leite F;Cordeiro JV;Handa Y;Arakawa Y;Valderrama F;Way M
通讯作者：
Way M
DOI：
10.1186/1478-811x-12-12
发表时间：
2014-03-04
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Amsellem V;Dryden NH;Martinelli R;Gavins F;Almagro LO;Birdsey GM;Haskard DO;Mason JC;Turowski P;Randi AM
通讯作者：
Randi AM
影响因子：
9.8
作者：
Bell CH;Aricescu AR;Jones EY;Siebold C
通讯作者：
Siebold C
影响因子：
9.2
作者：
Bravo-Cordero, Jose Javier;Oser, Matthew;Chen, Xiaoming;Eddy, Robert;Hodgson, Louis;Condeelis, John
通讯作者：
Condeelis, John
影响因子：
4
作者：
Amado-Azevedo, J.;Reinhard, N. R.;Hordijk, P. L.
通讯作者：
Hordijk, P. L.