Heparin-binding epidermal growth factor-like growth factor regulates fibroblast growth factor-2 expression in aortic smooth muscle cells.
Heparin-binding epidermal growth factor-like growth factor regulates fibroblast growth factor-2 expression in aortic smooth muscle cells.
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DOI：
10.1161/01.res.79.2.263
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发表时间：
1996-08
影响因子：
20.1
通讯作者：
K. Peifley;G. F. Alberts;D. K. Hsu;S. Feng;J. Winkles
中科院分区：
文献类型：
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作者：
K. Peifley;G. F. Alberts;D. K. Hsu;S. Feng;J. Winkles
肝素结合表皮生长因子样生长因子 (HB-EGF) 是一种血管平滑肌细胞 (SMC) 有丝分裂原和趋化因子，由内皮细胞、SMC、单核细胞/巨噬细胞和 T 淋巴细胞表达。膜锚定的HB-EGF前体和分泌的成熟HB-EGF蛋白均具有生物活性；因此，HB-EGF 可能通过自分泌、旁分泌和邻分泌机制刺激 SMC 生长。在本研究中，我们报道HB-EGF治疗主动脉SMC的血清饥饿可以诱导成纤维细胞生长因子（FGF）-2（碱性FGF）基因表达，但不诱导FGF-1（酸性FGF）基因表达。添加 HB-EGF 后 1 小时首次检测到 FGF-2 mRNA 表达增加，4 小时时出现最大 FGF-2 mRNA 水平，相当于诱导水平的约 46 倍。 HB-EGF 对 FGF-2 mRNA 水平的影响似乎主要由转录机制介导，并且需要从头合成蛋白质。用抗炎糖皮质激素地塞米松或糖胺聚糖肝素处理细胞可以抑制 HB-EGF 诱导的 FGF-2 mRNA 水平。最后，蛋白质印迹分析表明，经 HB-EGF 处理的 SMC 还产生数量增加的 FGF-2 蛋白。这些结果表明，体内血管损伤或炎症部位表达的 HB-EGF 可能上调 SMC 产生的 FGF-2。
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a vascular smooth muscle cell (SMC) mitogen and chemotactic factor that is expressed by endothelial cells, SMCs, monocytes/macrophages, and T lymphocytes. Both the membrane-anchored HB-EGF precursor and the secreted mature HB-EGF protein are biologically active; thus, HB-EGF may stimulate SMC growth via autocrine, paracrine, and juxtacrine mechanisms. In the present study, we report that HB-EGF treatment of serum-starved at aortic SMCs can induce fibroblast growth factor (FGF)-2 (basic FGF) gene expression but not FGF-1 (acidic FGF) gene expression. Increased FGF-2 mRNA expression is first detectable at 1 hour after HB-EGF addition, and maximal FGF-2 mRNA levels, corresponding to an approximately 46-fold level of induction, are present at 4 hours. The effect of HB-EGF on FGF-2 mRNA levels appears to be mediated primarily by a transcriptional mechanism and requires de novo synthesized proteins. HB-EGF induction of FGF-2 mRNA levels can be inhibited by treating cells with the anti-inflammatory glucocorticoid dexamethasone or the glycosaminoglycan heparin. Finally, Western blot analyses indicate that HB-EGF-treated SMCs also produce an increased amount of FGF-2 protein. These results indicate that HB-EGF expressed at sites of vascular injury or inflammation in vivo may upregulate FGF-2 production by SMCs.