Kruppel-like factor 15 regulates smooth muscle response to vascular injury--brief report.
Kruppel-like factor 15 regulates smooth muscle response to vascular injury--brief report.
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DOI：
10.1161/atvbaha.110.207050
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发表时间：
2010-08
期刊：
影响因子：
--
通讯作者：
Jain MK
中科院分区：
文献类型：
--
作者：
Lu Y;Haldar S;Croce K;Wang Y;Sakuma M;Morooka T;Wang B;Jeyaraj D;Gray SJ;Simon DI;Jain MK
血管平滑肌细胞通过一系列紧密协调的基因调控事件对机械损伤作出反应。Kruppel Like Factor 15 （KLF15）是一种锌指转录因子，在血管平滑肌细胞（VSMCs）中表达，但其在血管生物学中的作用尚不清楚。KLF15在动脉和静脉血管床均以VSMCs受限方式广泛表达。KLF15的表达在药理学和机械刺激下均显著降低。为了研究KLF15在血管损伤反应中的具体作用，我们对KLF15 - / -和野生型（WT）小鼠进行了股动脉钢丝损伤。KLF15 - / -小鼠新生内膜生长过度，有证据表明新生内膜内SMC增殖和迁移增加。与此一致的是，对离体vsmc的功能获得和功能丧失的研究表明，KLF15可以直接抑制SMC的增殖和迁移。这些数据首次确定了KLF15是一种新的VSMCs增殖和迁移抑制剂，并暗示该因子是血管损伤反应的关键调节因子。
Vascular smooth muscle cells respond to mechanical injury via tightly orchestrated series of gene regulatory events. Kruppel Like Factor 15 (KLF15) is a zinc finger transcriptional factor that is expressed in vascular smooth muscle cells (VSMCs), however its role in vascular biology is unknown. KLF15 is broadly expressed in both arterial and venous vascular beds in a VSMCs restricted fashion. KLF15 expression is markedly reduced by both pharmacologic and mechanical stimuli. To examine the specific role of KLF15 in the vascular response to injury, we performed femoral artery wire injury in KLF15−/− and wild type (WT) mice. KLF15−/− mice develop exaggerated neointimal growth, with evidence of increased SMC proliferation and migration within the neointima. In concordance, gain and loss of function studies in isolated VSMCs demonstrate that KLF15 can directly inhibit both SMC proliferation and migration. These data are first to identify KLF15 as a novel inhibitor of VSMCs proliferation and migration and implicate this factor as a critical regulator of the vascular response to injury.