Activation of the integrins alpha 5beta 1 and alpha v beta 3 and focal adhesion kinase (FAK) during arteriogenesis.
Activation of the integrins alpha 5beta 1 and alpha v beta 3 and focal adhesion kinase (FAK) during arteriogenesis.
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动脉生成过程中整合素 α 5β 1 和 α V β 3 以及粘着斑激酶 (FAK) 的激活。
DOI：
10.1007/s11010-008-9953-8
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发表时间：
2009-02
影响因子：
4.3
通讯作者：
Schaper, Wolfgang
中科院分区：
文献类型：
--
作者：
Cai, Wei-Jun;Li, Ming Bo;Wu, Xiaoqiong;Wu, Song;Zhu, Wu;Chen, Dan;Luo, Mingying;Eitenmueller, Inka;Kampmann, Andreas;Schaper, Jutta;Schaper, Wolfgang
平滑肌细胞（SMC）的迁移和增殖是动脉形成过程中的重要事件，但其机制仍不完全清楚。本研究通过共聚焦免疫荧光技术研究了整合素α5β1和vβ3以及粘着斑激酶（FAK）和磷酸化FAK（pY 397）在兔后肢侧支血管（CV）中的表达，这些细胞是细胞迁移和增殖的关键介质，这些侧支血管是由股动脉结扎或在远端股动脉残端和伴随的股静脉之间建立动静脉（AV）分流诱导的。此外，研究了细胞外基质成分纤连蛋白（FN）、层粘连蛋白（LN）和Matrigel对培养的SMC中这些粘着斑分子增殖表达的影响。我们发现：（1）在正常血管（NV）中，整合素α5β1和αvβ3主要表达于内皮细胞，平滑肌细胞（SMC）中表达很弱;（2）在CV中，整合素α5β1和αvβ3均显著上调（P < 0.05），其中以分流侧CV最明显，分别为结扎侧的1.5倍和1.3倍;（3）FAK和FAK（py 397）在NV和CV中的表达与α5β1和αvβ3的表达相似;（4）在纤连蛋白（在侧枝中过表达）上培养的体外SMC表达比在层粘连蛋白上更高水平的FAK、FAK（pY 397）、α5β1和αvβ3，而在Matrigel内生长的SMC几乎不表达这些蛋白，并且不显示增殖。总之，我们的数据首次表明，整合素FAK信号轴被激活的侧支血管和FN和LN的表达改变可能在介导整合素FAK信号通路的激活中起着至关重要的作用。这些发现解释了侧支血管在高流体切应力影响下发生的正性重塑的大部分原因。
Migration and proliferation of smooth muscle cells (SMC) are important events during arteriogenesis, but the underlying mechanism is still only partially understood. The present study investigates the expression of integrins α5β1 and vβ3 as well as focal adhesion kinase (FAK) and phosphorylated FAK (pY397), key mediators for cell migration and proliferation, in collateral vessels (CV) in rabbit hind limbs induced by femoral ligation or an arteriovenous (AV) shunt created between the distal femoral artery stump and the accompanying femoral vein by confocal immunofluorescence. In addition, the effect of the extracellular matrix components fibronectin (FN), laminin (LN), and Matrigel on expression of these focal adhesion molecules proliferation was studied in cultured SMCs. We found that: (1) in normal vessels (NV), both integrins α5β1 and αvβ3 were mainly expressed in endothelial cells, very weak in smooth muscle cells (SMC); (2) in CVs, both α5β1 and αvβ3 were significantly upregulated (P < 0.05); this was more evident in the shunt-side CVs, 1.5 and 1.3 times higher than that in the ligation side, respectively; (3) FAK and FAK(py397) were expressed in NVs and CVs in a similar profile as was α5β1 and αvβ3; (4) in vitro SMCs cultured on fibronectin (overexpressed in collaterals) expressed higher levels of FAK, FAK (pY397), α5β1, and αvβ3 than on laminin, whereas SMCs growing inside Matrigel expressed little of these proteins and showed no proliferation. In conclusion, our data demonstrate for the first time that the integrin-FAK signaling axis is activated in collateral vessels and that altered expression of FN and LN may play a crucial role in mediating the integrin-FAK signaling pathway activation. These findings explain a large part of the positive remodeling that collateral vessels undergo under the influence of high fluid shear stress.
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DOI：
10.1083/jcb.121.1.163
发表时间：
1993-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Leavesley DI;Schwartz MA;Rosenfeld M;Cheresh DA
通讯作者：
Cheresh DA
影响因子：
4.8
作者：
Ho, AT;Voura, EB;Khokha, R
通讯作者：
Khokha, R
影响因子：
64.5
作者：
Brooks, PC;Stromblad, S;Cheresh, DA
通讯作者：
Cheresh, DA
纤连蛋白和层粘连蛋白对培养的动脉平滑肌细胞表型特性的各种影响。
影响因子：
7.8
作者：
Hedin, U;Bottger, B A;Forsberg, E;Johansson, S;Thyberg, J
通讯作者：
Thyberg, J
影响因子：
4.8
作者：
Li, S;Kim, M;Shyy, JYJ
通讯作者：
Shyy, JYJ