Role of activating protein-1 and high mobility group-I(Y) protein in the induction of CD44 gene expression by interleukin-1β in vascular smooth muscle cells
Role of activating protein-1 and high mobility group-I(Y) protein in the induction of CD44 gene expression by interleukin-1β in vascular smooth muscle cells
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DOI：
10.1096/fasebj.14.2.368
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发表时间：
2000-02-01
期刊：
影响因子：
4.8
通讯作者：
Perrella, MA
中科院分区：
文献类型：
--
作者：
Foster, LC;Wiesel, P;Perrella, MA
CD 44是一种多功能细胞粘附分子，参与炎症和肿瘤发生等病理状态。CD 44在动脉壁损伤后的血管平滑肌细胞上被诱导，并可能介导动脉硬化期间它们的增殖和迁移到新生内膜中。我们在其他地方已经证明，促炎细胞因子白细胞介素（IL）-1 β通过增加基因转录上调培养的大鼠主动脉平滑肌细胞（RASMC）中的CD 44 mRNA和蛋白表达。通过将5 ′-缺失构建体瞬时转染到RASMC中，我们在本研究中表明，距离小鼠CD 44启动子转录起始位点110个碱基对的保守AP-1位点对基础活性是重要的，AP-1位点的突变显著降低了IL-1 β对启动子活性的诱导，和电泳迁移率变动分析表明，Fos和c-Jun在IL-1 β刺激后存在于CD 44 AP-1结合复合物中，此外，结构转录因子高迁移率族（HMG）-I（Y）蛋白与c-Fos和c-Jun的共转染显著增加了CD 44启动子的反式激活。总之，我们的研究表明AP-1蛋白是IL-1 β在血管平滑肌细胞炎症反应期间调节CD 44表达的中心调节组分，并且HMG-1（Y）增强AP-1蛋白对CD 44的转录。
CD44 is a multifunctional cell adhesion molecule that participates in pathological states such as inflammation and tumorigenesis. CD44 is induced on vascular smooth muscle cells after arterial wall injury and may mediate their proliferation and migration into the neointima during arteriosclerosis. We have demonstrated elsewhere that the proinflammatory cytokine interleukin (IL)-1 beta upregulates CD44 mRNA and protein expression in cultured rat aortic smooth muscle cells (RASMC) by increasing gene transcription. By transient transfection of 5'-deletion constructs into RASMC, we show in the present study that a conserved AP-1 site 110 base pairs from the transcription start site of the mouse CD44 promoter is important for basal activity, Mutation of the AP-1 site significantly reduced induction of promoter activity by IL-1 beta, and electrophoretic mobility shift assays demonstrated that Fos and c-Jun were present in the CD44 AP-1 binding complex after IL-1 beta stimulation, in addition, cotransfection of the architectural transcription factor high mobility group (HMG)-I(Y) protein with c-Fos and c-Jun markedly increased trans-activation of the CD44 promoter, Taken together, our studies demonstrate that AP-1 proteins are a central regulatory component used by IL-1 beta to modulate expression of CD44 during an inflammatory response in vascular smooth muscle cells and that transcription of CD44 by AP-1 proteins is enhanced by HMG-1(Y).