Retinoid receptor expression and all-trans retinoic acid-mediated growth inhibition in vascular smooth muscle cells
Retinoid receptor expression and all-trans retinoic acid-mediated growth inhibition in vascular smooth muscle cells
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DOI：
10.1161/01.cir.93.10.1886
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发表时间：
1996-05-15
期刊：
影响因子：
37.8
通讯作者：
Olson, EN
中科院分区：
文献类型：
--
作者：
Miano, JM;Topouzis, S;Olson, EN
背景类维生素A已成功用于治疗多种人类过度增殖性疾病。然而，它们在平滑肌细胞（SMC）生长控制中的作用尚未明确。本研究的目的是评估的维甲酸受体mRNA的表达谱在SMCs，并确定是否维甲酸发挥生长抑制作用，在这些cells.Methods和结果5的6维甲酸受体表达在培养的SMCs和主动脉作为确定由北方印迹或逆转录-聚合酶链反应。受体活性在SMC中被证明与使用的报告分析与连接到氯霉素乙酰转移酶报告基因的维甲酸受体DNA结合序列。DNA合成和细胞增殖试验表明，全反式维甲酸（atRA）拮抗血小板衍生生长因子-BB和血清刺激SMC的生长。生长抑制是远端的早期生长信号事件，因为诱导c-fos，c-jun，和c-fos-1 mRNA是不受atRA。然而，与激活的蛋白-1-连接氯霉素乙酰转移酶报告; atRA被证明抑制活性的激活蛋白-1-依赖的转录在瞬时transfection assay.Conclusions这些结果建立的存在下，功能性维甲酸受体在SMC和文件的生长抑制作用atRA对这些细胞。类维生素A化合物，已经在临床上用作抗增殖剂的非血管适应症，应进一步评估在体内模型内膜疾病。
Background Retinoids have been used in the successful treatment of a variety of human hyperproliferative diseases. Their role in smooth muscle cell (SMC) growth control, however, has not been clearly established. The present study was designed to assess the retinoid receptor mRNA expression profile in SMCs and to determine whether retinoids exert a growth-inhibitory effect in these cells.Methods and Results Five of the six retinoid receptors were expressed in both cultured SMCs and aorta as determined by Northern blotting or reverse transcription-polymerase chain reaction. Receptor activity was demonstrated in SMCs with the use of a reporter assay with a retinoid receptor DNA binding sequence linked to a chloramphenicol acetyltransferase reporter gene. DNA synthesis and cell proliferation assays were performed to show that all-trans retinoic acid (atRA) antagonized platelet-derived growth factor-BB and serum-stimulated SMC growth. Growth inhibition was distal to early growth-signaling events because induction of c-fos, c-jun, and egr-1 mRNA was unaffected by atRA. However, with an activated protein-1-linked chloramphenicol acetyltransferase reporter; atRA was shown to inhibit the activity of activated protein-1-dependent transcription in a transient transfection assay.Conclusions These results establish the presence of functional retinoid receptors in SMCs and document the growth-inhibitory action of atRA on these cells. Retinoid compounds, already in clinical use as antiproliferative agents for nonvascular indications, should be assessed further in in vivo models of intimal disease.