Upregulation of decorin by FXR in vascular smooth muscle cells
Upregulation of decorin by FXR in vascular smooth muscle cells
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FXR 对血管平滑肌细胞中核心蛋白聚糖的上调
DOI：
10.1016/j.bbrc.2008.05.098
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发表时间：
2008-08-08
影响因子：
3.1
通讯作者：
Li, Song
中科院分区：
文献类型：
--
作者：
He, Fengtian;Zhang, Qiuhong;Li, Song
核心蛋白聚糖是存在于血管中并由血管平滑肌细胞（VSMC）合成的富含亮氨酸的小蛋白聚糖家族的成员。核心蛋白聚糖在正常的血管生理学和各种类型的血管疾病的发病机制中起着复杂的作用。然而，核心蛋白聚糖在血管中表达的调控机制尚不清楚。关于核受体在核心蛋白聚糖表达调节中的作用，特别是可用的信息很少。在本研究中，我们报告说，血管FXR的激活由一个特定的配体导致上调核心蛋白聚糖在mRNA和蛋白质水平。FXR似乎在转录水平上诱导核心蛋白聚糖表达，因为（1）核心蛋白聚糖mRNA表达的上调被转录抑制剂放线菌素D的处理消除;和（2）核心蛋白聚糖启动子活性通过FXR的活化显著增加。对人核心蛋白聚糖启动子的功能分析鉴定了不完全反向重复DNA基序IR 8（-2313TGGTCAtagtgtcaTGACCT-2294），其可能是参与核心蛋白聚糖调控的FXR应答元件。(c)2008年爱思唯尔公司All rights reserved.
Decorin is a member of the family of small leucine-rich proteoglycans that are present in blood vessels and synthesized by vascular smooth muscle cells (VSMCs). Decorin plays complex roles in both normal vascular physiology and the pathogenesis of various types of vascular disorders. However, the mechanisms of regulation of decorin expression in vasculature are not clearly understood. Particularly little information is available about a role of nuclear receptors in the regulation of decorin expression. In the present study, we report that activation of vascular FXR by a specific ligand resulted in upregulation of decorin at the levels of both mRNA and protein. FXR appears to induce decorin expression at a transcriptional level because (1) upregulation of decorin mRNA expression was abolished by the treatment of a transcription inhibitor, actinomycin D; and (2) decorin promoter activity was significantly increased by activation of FXR. Functional analysis of human decorin promoter identified an imperfect inverted repeat DNA motif, IR8 (-2313TGGTCAtagtgtcaTGACCT-2294), as a likely FXR-responsive element that is involved in decorin regulation. (c) 2008 Elsevier Inc. All rights reserved.