Hepatocyte Growth Factor/Scatter Factor (HGF/SF) Induces Vascular Permeability Factor (VPF/VEGF) Expression by Cultured Keratinocytes
| Autor: | Mona Khalik, Roland Kaufmann, Jens Gille, Veronika König |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Keratinocytes
Vascular Endothelial Growth Factor A medicine.medical_specialty Angiogenesis Gene Expression Endothelial Growth Factors Dermatology Biology Biochemistry Cell Line chemistry.chemical_compound Paracrine signalling Internal medicine medicine Humans RNA Messenger Cycloheximide Phosphorylation Molecular Biology Protein Synthesis Inhibitors Regulation of gene expression Lymphokines Hepatocyte Growth Factor Vascular Endothelial Growth Factors Cell Biology Fibroblasts Genistein Growth Inhibitors Up-Regulation Vascular endothelial growth factor Vascular endothelial growth factor A medicine.anatomical_structure Endocrinology chemistry Cancer research Tyrosine Hepatocyte growth factor 5' Untranslated Regions Keratinocyte Wound healing medicine.drug |
| Zdroj: | Journal of Investigative Dermatology. 111:1160-1165 |
| ISSN: | 0022-202X |
| Popis: | 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 to 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|