Different growth properties of neointimal and medial smooth muscle cells in response to growth factors

Different growth properties of neointimal and medial smooth muscle cells in response to growth factors
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DOI:
10.1159/000070706
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发表时间:
2003-03-01
影响因子:
1.7
通讯作者:
Brink, M
Brink, M
中科院分区:
医学4区
文献类型:
--
作者:
Myit, S;Delafontaine, P;Brink, M

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不同的平滑肌细胞表型在动脉中共存。从正常大鼠主动脉中培养的大多数细胞具有梭形表型,而从内皮损伤后15天的内膜增厚中分离的细胞显示出独特的上皮样表型。这两种表型表达它们自己的特定基因组,并且在它们的增殖和迁移特征上不同。我们研究了两种表型中生长因子诱导的DNA合成,并研究了生长特征差异背后的潜在机制。胰岛素样生长因子-I(IGF-I),血小板源性生长因子(PDGF-BB),和碱性成纤维细胞生长因子(FGF)增加胸苷掺入在两种表型,但增加显着强于新生内膜细胞中的中膜细胞。北方印迹分析30分钟后,生长因子刺激表明,c-fos和c-jun mRNA的诱导更强烈的新生内膜比中膜细胞。IGF-I受体和PDGF-R β水平在新生内膜细胞中高于中膜细胞,但FGF受体水平在细胞类型之间没有差异。总之,我们的研究结果表明,新生内膜细胞比中膜细胞对生长因子更敏感,这可能是由于IGF-I受体和PDGF-R β的表达更高。我们的研究结果提供了深入了解上皮样细胞在血管新生内膜形成中发挥主要作用的机制。版权所有(C)2003 S. Karger AG,巴塞尔。
Different smooth muscle cell phenotypes coexist in arteries. The majority of cells cultured from a normal rat aortic media have a spindle-shaped phenotype while cells isolated from an intimal thickening 15 days after endothelial injury show a distinct epithelioid phenotype. These two phenotypes express their own specific set of genes and differ in their proliferation and migration characteristics. We studied growth factor-induced DNA synthesis in both phenotypes and investigated the potential mechanisms behind the differences in growth characteristics. Insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF-BB), and basic fibroblast growth factor (FGF) increased thymidine incorporation in both phenotypes, but the increase was markedly stronger in neointimal cells than in medial cells. Northern blot analysis 30 min after growth factor stimulation showed that c-fos and c-jun mRNAs were induced more strongly in neointimal than in medial cells. IGF-I receptor and PDGF-Rbeta levels were higher in neointimal cells than in medial cells, but the FGF receptor level was not different between the cell types. In summary, our results indicate that neointimal cells are more sensitive to growth factors than medial cells, likely due to a higher expression of IGF-I receptor and PDGF-Rbeta. Our results provide insight into the mechanism by which epithelioid cells play a primary role in vascular neointima formation. Copyright (C) 2003 S. Karger AG, Basel.