FRNK expression promotes smooth muscle cell maturation during vascular development and after vascular injury.
FRNK expression promotes smooth muscle cell maturation during vascular development and after vascular injury.
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DOI：
10.1161/atvbaha.108.175455
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发表时间：
2008-12
期刊：
影响因子：
--
通讯作者：
Taylor JM
中科院分区：
文献类型：
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作者：
Sayers RL;Sundberg-Smith LJ;Rojas M;Hayasaka H;Parsons JT;Mack CP;Taylor JM
平滑肌细胞（SMC）的分化是一个动态的过程，必须严格调节适当的血管发育和控制血管疾病的发生。我们的实验室先前报道了一种称为FRNK（FAK相关非激酶）的特异性粘着斑激酶（FAK）抑制剂在SMC从合成表型向收缩表型转变时选择性地在大动脉中表达，并且FRNK抑制FAK依赖性SMC增殖和迁移。在此，我们试图确定是否FRNK表达调节SMC表型在体内。我们提供的证据表明，FRNK-/-小鼠在出生后血管生长和血管损伤期间表现出SM标记基因表达减弱。我们还发现FRNK的表达受TGF-β的调节，并且在培养的细胞中FRNK的强制表达诱导血清和TGF-β刺激的SM标记基因的表达，而FRNK缺失或组成性激活的FAK变体的表达减弱SM基因的转录。这些数据突出的可能性，外源性信号调节SMC基因谱，至少部分地，通过调节FRNK的表达和FAK活性的严格调节FRNK是重要的适当的SMC分化过程中的发展和血管损伤后。
Smooth muscle cell (SMC) differentiation is a dynamic process that must be tightly regulated for proper vascular development and to control the onset of vascular disease. Our lab previously reported that a specific focal adhesion kinase (FAK) inhibitor termed FRNK (FAK Related Non-Kinase) is selectively expressed in large arterioles when SMC are transitioning from a synthetic to contractile phenotype and that FRNK inhibits FAK-dependent SMC proliferation and migration. Herein, we sought to determine whether FRNK expression modulates SMC phenotypes in vivo. We present evidence that FRNK−/− mice exhibit attenuated SM marker gene expression during post-natal vessel growth and following vascular injury. We also show that FRNK expression is regulated by TGF-β and that forced expression of FRNK in cultured cells induces serum- and TGF-β-stimulated SM marker gene expression, while FRNK deletion or expression of a constitutively activated FAK variant attenuated SM gene transcription. These data highlight the possibility that extrinsic signals regulate the SMC gene profile, at least in part, by modulating the expression of FRNK and that tight regulation of FAK activity by FRNK is important for proper SMC differentiation during development and following vascular injury.