PMID- 9856833
OWN - NLM
STAT- MEDLINE
DCOM- 19990104
LR  - 20131121
IS  - 0022-202X (Print)
IS  - 0022-202X (Linking)
VI  - 111
IP  - 6
DP  - 1998 Dec
TI  - Hepatocyte growth factor/scatter factor (HGF/SF) induces vascular permeability 
      factor (VPF/VEGF) expression by cultured keratinocytes.
PG  - 1160-5
AB  - 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.
FAU - Gille, J
AU  - Gille J
AD  - Zentrum der Dermatologie, Klinikum der J.W. Goethe-Universitat, Frankfurt am 
      Main, Germany.
FAU - Khalik, M
AU  - Khalik M
FAU - Konig, V
AU  - Konig V
FAU - Kaufmann, R
AU  - Kaufmann R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (Growth Inhibitors)
RN  - 0 (Lymphokines)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - 42HK56048U (Tyrosine)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 98600C0908 (Cycloheximide)
RN  - DH2M523P0H (Genistein)
SB  - IM
MH  - 5' Untranslated Regions
MH  - Cell Line
MH  - Cycloheximide/pharmacology
MH  - Endothelial Growth Factors/chemistry/*genetics
MH  - Fibroblasts/metabolism
MH  - Gene Expression/drug effects
MH  - Genistein/pharmacology
MH  - Growth Inhibitors/pharmacology
MH  - Hepatocyte Growth Factor/*pharmacology
MH  - Humans
MH  - Keratinocytes/cytology/*metabolism
MH  - Lymphokines/chemistry/*genetics
MH  - Phosphorylation/drug effects
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Tyrosine
MH  - Up-Regulation
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
EDAT- 1998/12/18 00:00
MHDA- 1998/12/18 00:01
CRDT- 1998/12/18 00:00
PHST- 1998/12/18 00:00 [pubmed]
PHST- 1998/12/18 00:01 [medline]
PHST- 1998/12/18 00:00 [entrez]
AID - S0022-202X(15)40334-3 [pii]
AID - 10.1046/j.1523-1747.1998.00418.x [doi]
PST - ppublish
SO  - J Invest Dermatol. 1998 Dec;111(6):1160-5. doi: 10.1046/j.1523-1747.1998.00418.x.