Basic fibroblast growth factor decreases elastin gene transcription in aortic smooth muscle cells
Basic fibroblast growth factor decreases elastin gene transcription in aortic smooth muscle cells
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DOI：
10.1002/jcb.10163
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发表时间：
2002-01-01
影响因子：
4
通讯作者：
Foster, JA
中科院分区：
文献类型：
--
作者：
Carreras, I;Rich, CB;Foster, JA
细胞外基质（ECM）蛋白弹性蛋白通过赋予血管壁弹性而在心血管系统中起重要作用。在这项研究中，我们研究了碱性成纤维细胞生长因子（bFGF）对主动脉平滑肌细胞（SMC）弹性蛋白表达的影响，以深入了解与心血管疾病相关的事件。结果表明，bFGF治疗SMC引起弹性蛋白mRNA和分泌的弹性蛋白原水平的显着下降。核连续分析表明，下调它，由于弹性蛋白基因转录水平的下降。用野生型和突变的弹性蛋白基因启动子/氯霉素乙酰转移酶（CAT）构建体瞬时转染SMC表明，先前鉴定的弹性蛋白启动子内的激活蛋白-1-cAMP应答元件（AP 1/CRE）（-564至-558-bp）介导了SMC中弹性蛋白基因转录的bFGF依赖性下调。向SMC中添加bFGF激活细胞外信号调节激酶1/2（ERK 1/2），导致其易位到细胞核中并随后诱导Fra-1。加入ERK 1/2激酶抑制剂PD-98059，消除了bFGF依赖的SMC中弹性蛋白mRNA的减少。所述bFGF对SMC中弹性蛋白基因表达的抑制作用可能显著有助于血管壁损伤早期弹性蛋白的无效修复。
The extracellular matrix (ECM) protein elastin plays an essential role in the cardiovascular system by imparting elasticity to blood vessel wall. In this study, we examined the effect of basic fibroblast growth factor (bFGF) on the expression of elastin in aortic smooth muscle cells (SMC) to gain insight into events associated with cardiovascular diseases. The results show that bFGF treatment of SMC causes a significant decrease in elastin mRNA and secreted tropoelastin levels. Nuclear run-on analyses demonstrate that the downregulation it, due to a decrease in the level of elastin gene transcription. Transient transfections of SMC with wild-type and mutated elastin gene promoter/chloramphenicol acetyl transferase (CAT) constructs show that a previously identified activator protein-1-cAMP response elemen: (AP1/CRE) (-564 to -558-bp) within the elastin promoter mediates the bFGF-dependent downregulation of elastin gene transcription in SMC. Addition of bFGF to SMC activates the extracellular signal-regulated kinases 1/2 (ERK1/2) resulting in their translocation into the nucleus and subsequent induction of Fra-1. The addition of PD-98059, an inhibitor of ERK1/2 kinase, abrogates the bFGF-dependent decrease of elastin mRNA in SMC, The described inhibitory effect of bFGF on elastin gene expression in SMC may significantly contribute to the inefficient repair of elastin in early stages of vascular wall injury.