Evaluation of the physiological significance of botrocetin/ von Willebrand factor in vitro signaling.
Evaluation of the physiological significance of botrocetin/ von Willebrand factor in vitro signaling.
复制标题
DOI：
10.1111/j.1538-7836.2008.03135.x
复制
发表时间：
2008-11
期刊：
影响因子：
--
通讯作者：
Gartner TK
中科院分区：
文献类型：
--
作者：
Liu J;Joglekar M;Ware J;Fitzgerald ME;Lowell CA;Berndt MC;Gartner TK
仅使用体内研究，很难（如果不是不可能的话）阐明血小板中的信号传导途径。同样地，仅从体外观察获得的信号信息的生理意义是未知的。因此，需要体外和体内实验来建立信号通路的生理意义。目的评价肉毒素（botrocetin，bt）/血管性血友病因子（vonWillebrand factor，VWF）刺激的洗涤血小板信号转导数据的生理意义。响应于FeCl 3诱导的小鼠颈动脉损伤的稳定血栓形成被用于评估从bt/VWF刺激的洗涤的血小板获得的信号数据的生理意义。Syk、PLC γ 2、G α q和P2Y12是稳定血栓形成所必需的或影响血栓形成的因素，而LAT则不是。先前的体外研究已经证明，在外源性纤维蛋白原存在的情况下，bt/VWF诱导的血小板聚集不需要LAT。这些数据首次证明了这些信号分子在GPIb依赖性/启动的信号转导中的体内作用，并且与使用代谢抑制剂和基因敲除小鼠从bt/VWF刺激的洗涤血小板的体外研究中推导出的信号通路一致。在体外和体内的结果之间的广泛的协议建立，bt/VWF刺激洗涤血小板可以提供生理上显着的糖蛋白Ib依赖/启动信号数据。
A signaling pathway is difficult, if not impossible, to elucidate in platelets using only in vivo studies. Likewise, the physiological significance of signaling information obtained exclusively from in vitro observations is unknown. Therefore, both in vitro and in vivo experiments are required to establish the physiological significance of a signaling pathway. To evaluate the physiological significance of signaling data obtained from botrocetin (bt)/von Willebrand factor (VWF)-stimulated washed platelets. Stable thrombus formation in response to FeCl3-induced injury of the mouse carotid artery was used to evaluate the physiological significance of signaling data obtained from bt/VWF-stimulated washed platelets. Syk, PLCγ2, Gαq and P2Y12, but not LAT, were found either to be required for or to affect stable thrombus formation. Prior in vitro studies had demonstrated that LAT is not required for bt/VWF-induced platelet aggregation in the presence of exogenous fibrinogen. These data provide the first demonstration of the in vivo role for these signaling molecules in GPIb-dependent/initiated signal transduction and are consistent with the signaling pathway deduced from in vitro studies of bt/VWF-stimulated washed platelets using metabolic inhibitors and knockout mice. The broad agreement between the in vitro and the in vivo results establish that bt/VWF stimulation of washed platelets can provide physiologically significant glycoprotein Ib-dependent/initiated signaling data.
登录
查看更多内容
整联蛋白alpha2beta1通过激活SRC激酶和PLCGAMMA2介导胶原蛋白上血小板扩散的外部调节。
DOI：
10.1083/jcb.200208043
发表时间：
2003-03-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Inoue O;Suzuki-Inoue K;Dean WL;Frampton J;Watson SP
通讯作者：
Watson SP
影响因子：
4.8
作者：
Mangin, P;Yuan, YP;Lanza, F
通讯作者：
Lanza, F
影响因子：
20.3
作者：
Kanaji, T;Russell, S;Ware, J
通讯作者：
Ware, J
影响因子：
82.9
作者：
Moers, A;Nieswandt, B;Offermanns, S
通讯作者：
Offermanns, S
影响因子：
3.2
作者：
Du, Xiaoping
通讯作者：
Du, Xiaoping