Periostin mediates vascular smooth muscle cell migration through the integrins alphavbeta3 and alphavbeta5 and focal adhesion kinase (FAK) pathway.
Periostin mediates vascular smooth muscle cell migration through the integrins alphavbeta3 and alphavbeta5 and focal adhesion kinase (FAK) pathway.
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DOI：
10.1016/j.atherosclerosis.2009.07.046
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发表时间：
2010-02
期刊：
影响因子：
5.3
通讯作者：
Granger, D. Neil
中科院分区：
文献类型：
--
作者：
Li, Guohong;Jin, Rong;Norris, Russell A.;Zhang, Lin;Yu, Shiyong;Wu, Fusheng;Markwald, Roger R.;Nanda, Anil;Conway, Simon J.;Smyth, Susan S.;Granger, D. Neil
平滑肌细胞（SMC）迁移涉及整合素受体与细胞外基质（ECM）的相互作用，是血管干预后动脉粥样硬化和再狭窄中新内膜形成的重要过程。先前的研究表明，大鼠颈动脉球囊损伤后，一种新型ECM蛋白——骨膜蛋白（periostin， PN）在体外表达上调，生长因子刺激下的PN表达促进了SMC的迁移。在这里，我们探讨了pn -整合素相互作用介导SMC在体外迁移的机制。从PN缺失小鼠分离的主动脉SMCs显示出明显降低的体外迁移和增殖能力。在原代培养和野生型SMCs的培养基中，内源性PN蛋白分别缺失和极低。在这两种类型的SMCs中，腺病毒介导的ha标记PN的过表达程度相似，诱导了强大的细胞迁移，同时增加了β3-整合素的表达和FAK的磷酸化（Tyr397）。此外，在培养的人SMCs中，特异性整合素阻断抗体显示，SMC迁移需要PN-ανβ3和PN-ανβ5的相互作用，而不需要PN-β1整合素。通过过表达内源性FAK抑制剂FRNK （FAK相关非激酶）抑制FAK信号传导，可显著减弱FAK （Tyr397）磷酸化和PN诱导的SMC迁移。这些结果揭示了PN通过与α - v整合素（主要是ανβ3）相互作用以及随后激活FAK途径介导血管SMC迁移的机制。
Smooth muscle cell (SMC) migration involves interactions of integrin receptors with extracellular matrix (ECM) and is an important process of neointimal formation in atherosclerosis and restenosis after vascular interventions. Previous studies have shown that periostin (PN), a novel ECM protein, is upregulated in rat carotid artery after balloon injury, and growth factor-stimulated expression of PN promotes SMC migration in vitro. Here, we address the mechanism by which PN–integrin interaction mediates SMC migration in vitro. Aortic SMCs isolated from PN null mice exhibited a significantly reduced ability to migrate and proliferate in vitro. Endogenous PN protein was absent and very low in the culture medium from the primary cultures of PN−/− and wildtype SMCs, respectively. In both types of SMCs, adenovirus-mediated overexpression of HA-tagged PN to a similar extent, which induced a robust cell migration concomitantly with an increase in β3-integrin expression and phosphorylation of FAK (Tyr397). Furthermore, in cultured human SMCs, specific integrin blocking antibodies showed that interactions of PN-ανβ3 and PN-ανβ5, but not PN-β1 integrins, are required for SMC migration. Inhibition of FAK signaling by overexpression of an endogenous FAK inhibitor termed FRNK (FAK-related nonkinase) significantly attenuated FAK (Tyr397) phosphorylation and the SMC migration induced by PN. These results reveal a mechanism whereby PN mediates vascular SMC migration through an interaction with alphaV-integrins (mainly ανβ3) and subsequent activation of FAK pathway.
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影响因子：
5.3
作者：
Shao, R;Bao, SD;Wang, XF
通讯作者：
Wang, XF
DOI：
10.1196/annals.1420.005
发表时间：
2008-01-01
期刊：
CONTROL AND REGULATION OF TRANSPORT PHENOMENA IN THE CARDIAC SYSTEM
影响因子：
--
作者：
Norris, Russell A.;Borg, Thomas K.;Markwald, Roger R.
通讯作者：
Markwald, Roger R.
影响因子：
3.7
作者：
Han, Mei;Wen, Jin-Kun;Chen, Yunhui
通讯作者：
Chen, Yunhui
影响因子：
4.3
作者：
Kokubo, Taku;Uchida, Hisashi;Choi, Eric T.
通讯作者：
Choi, Eric T.
DOI：
10.1161/01.atv.0000149141.81230.c6
发表时间：
2005-01-01
影响因子：
8.7
作者：
Lindner, V;Wang, QZ;Vary, CPH
通讯作者：
Vary, CPH