Phenotypic Modulation of Vascular Smooth Muscle Cells
Phenotypic Modulation of Vascular Smooth Muscle Cells
复制标题
血管平滑肌细胞的表型调节
DOI：
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发表时间：
2001
影响因子：
5.2
通讯作者：
M. Kurabayashi
中科院分区：
文献类型：
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作者：
R. Nagai;Toru Suzuki;K. Aizawa;S. Miyamoto;T. Amaki;K. Kawai;K. Sekiguchi;M. Kurabayashi
翻译后摘要：平滑肌肌球蛋白重链（MHC）基因及其亚型是很好的分子标记，反映平滑肌表型。SMem B/非肌肉肌球蛋白重链B（NMHC-B）是一种独特的MHC基因，主要在表型调节的SMC（合成型SMC）中表达。为了剖析SMC表型调控的分子机制，我们分析了SMemb基因表达的转录调控机制。我们以前报道了两个转录因子，BTEB 2/IKLF和Hex，其基于瞬时报告基因转染测定反式激活SMemb基因启动子。BTEB 2/IKLF是锌指转录因子，而Hex是同源异型盒蛋白。BTEB 2/IKLF在SMC中的表达随着体内血管的发育而下调，但在培养的SMC和球囊血管成形术后血管损伤的新生内膜中上调。BTEB 2/IKLF和Hex不仅激活SMemb基因，还激活合成SMC中激活的其他基因，包括纤溶酶原激活物抑制剂-1（派-1）、iNOS、PDGF-A、Egr-1和VEGF受体。促有丝分裂刺激通过MEK 1和Egr-1激活BTEB 2/IKLF基因表达。细胞内cAMP的升高在SMC的表型调节中也很重要，因为SMemb启动子在cAMP反应元件结合蛋白（CREB）和Hex的协同作用下被激活。
Abstract: The smooth muscle myosin heavy chain (MHC) gene and its isoforms are excellent molecular markers that reflect smooth muscle phenotypes. The SMemb/Nonmuscle Myosin Heavy Chain B (NMHC‐B) is a distinct MHC gene expressed predominantly in phenotypically modulated SMCs (synthetic‐type SMC). To dissect the molecular mechanisms governing phenotypic modulation of SMCs, we analyzed the transcriptional regulatory mechanisms underlying expression of the SMemb gene. We previously reported two transcription factors, BTEB2/IKLF and Hex, which transactivate the SMemb gene promoter based on the transient reporter transfection assays. BTEB2/IKLF is a zinc finger transcription factor, whereas Hex is a homeobox protein. BTEB2/IKLF expression in SMCs is downregulated with vascular development in vivo but upregulated in cultured SMCs and in neointima in response to vascular injury after balloon angioplasty. BTEB2/IKLF and Hex activate not only the SMemb gene but also other genes activated in synthetic SMCs including plasminogen activator inhibitor‐1 (PAI‐1), iNOS, PDGF‐A, Egr‐1, and VEGF receptors. Mitogenic stimulation activates BTEB2/IKLF gene expression through MEK1 and Egr‐1. Elevation of intracellular cAMP is also important in phenotypic modulation of SMCs, because the SMemb promoter is activated under cooperatively by cAMP‐response element binding protein (CREB) and Hex.