Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1999-7-7
pubmed:abstractText
Angiogenesis and the formation of new blood vessels requires coordinated regulation of matrix proteolysis and endothelial cell migration. Cellular proteolytic capacity is the balance between secreted matrix metalloproteinases (MMP) and their inhibitors (TIMPs). We have examined the regulation of the gelatinase/TIMP balance by transforming growth factor-beta1 (TGF-beta1) and phorbol myristate acetate (PMA) in bovine endothelial cells. The low constitutive expression of gelatinase A/MMP-2 was upregulated by TGF-beta1 in a dose-dependent manner. Gelatinase B/MMP-9 was only detected upon treatment with either PMA or TGF-beta1. However, addition of both factors together revealed a striking synergistic effect causing upregulation of MMP-9 and downregulation of TIMPs, thereby increasing the net MMP-9/TIMP balance and the gelatinolytic capacity. These effects were observed at both the protein and mRNA levels. We demonstrate that changes in different members of the Jun oncogene family with distinct transactivation properties may account for this synergistic effect. We investigated the contribution of these changes in gelatinolytic balance to endothelial cell migration and invasion. The endothelial cells showed increased cell motility in response to PMA, but the addition of TGF-beta1 had an inhibitory effect. Hence, regulation of the MMP-9/TIMP balance failed to correlate with the migratory or invasive capacity. These results question a direct role for MMP-9 in endothelial cell motility and suggest that gelatinases may contribute in alternative ways to the angiogenic process.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:volume
112 ( Pt 9)
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1283-90
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Examining the relationship between the gelatinolytic balance and the invasive capacity of endothelial cells.
pubmed:affiliation
U353 INSERM, Hôpital Saint Louis, France. s.menashi@chu-stlouis.fr.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't