Hepatocyte growth factor scatter factor (HGF/SF) induces vascular permeability factor (VPF/VEGF) expression by cultured keratinocytes
Hepatocyte growth factor scatter factor (HGF/SF) induces vascular permeability factor (VPF/VEGF) expression by cultured keratinocytes
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DOI：
10.1046/j.1523-1747.1998.00418.x
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发表时间：
1998-12-01
影响因子：
6.5
通讯作者：
Kaufmann, R
中科院分区：
文献类型：
--
作者：
Gille, J;Khalik, M;Kaufmann, R
皮肤表达的内皮细胞特异性血管通透性因子/血管内皮生长因子（VPF/VEGF）作为一个突出的调解人的生理和病理性血管生成已被证明是受不同的刺激调节。我们探讨了多功能肝细胞生长因子/分散因子（HGF/SF）是否可以通过旁分泌诱导皮肤VPF/VEGF合成来介导其血管生成特性。在这些研究中，我们证明，HGF/SF功能作为一个有效的诱导剂VPF/VEGF表达的人表皮角质形成细胞和不同的上皮来源的细胞在体外。VPF/VEGF mRNA和蛋白表达受HGF/SF以浓度和时间依赖性方式调节。mRNA半衰期的检查未显示HGF/SF刺激后VPF/VEGF mRNA稳定性增加。因此，HGF/SF诱导的VPF/VEGF mRNA表达似乎在很大程度上依赖于增强的基因转录。在对瞬时转染的5 ′-缺失报告基因构建体的分析中，我们鉴定了富含GC的VPF/VEGF启动子元件，其在应答Co HGF/SF时传递转录激活。该序列位于核苷酸-88和-70之间，对于组成型和HGF/SF诱导的转录活性都是关键的。总之，我们的观察结果支持一个模型，其中HGF/SF介导的血管生成特性的一部分，通过旁分泌诱导VPF/VEGF合成的角质形成细胞。除了皮肤炎症和伤口愈合外，我们的发现对肿瘤生长中的血管通透性过高和血管生成具有潜在意义。
Skin expression of the endothelial cell-specific vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) as an outstanding mediator of physiologic and pathologic angiogenesis has been previously demonstrated to be subject to regulation by distinct stimuli. We explored whether the multifunctional hepatocyte growth factor/scatter factor (HGF/SF) may mediate its angiogenic properties in part through paracrine induction of cutaneous VPF/VEGF synthesis. In these studies, we demonstrate that HGF/SF functions as a potent inducer of VPF/VEGF expression by human epidermal keratinocytes and by different epithelial-derived cells in vitro. VPF/VEGF mRNA and protein expression are regulated by HGF/SF in both a concentration- and a time-dependent fashion. Examination of mRNA half-lives does not reveal an increase in VPF/VEGF mRNA stability after HGF/SF stimulation. Thus, HGF/SF-induced VPF/VEGF mRNA expression appears to be largely dependent on enhanced gene transcription. In analyses of transiently transfected 5'-deletional reporter gene constructs, we identified a GC-rich VPF/VEGF promoter element that conveys transcriptional activation in response Co HGF/SF, This sequence, located between nucleotides -88 and -70, is critical for both constitutive and HGF/SF-induced transcriptional activity. Together, our observations support a model in which HGF/SF mediates angiogenic properties in part through paracrine induction of VPF/VEGF synthesis by keratinocytes. In addition to cutaneous inflammation and wound healing, our findings have potential significance for vascular hyperpermeability and angiogenesis in tumor growth.