Linked Life Data

10861846

Source:http://linkedlifedata.com/resource/pubmed/id/10861846

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-8-24
pubmed:abstractText
A coordinated interaction between fibroblast growth factors (FGFs) and matrix metalloproteinases (MMPs) is implicated in migration of microvascular endothelial cells (ECs), an early stage of angiogenesis. Specifically, we investigated microvascular ECs migration in vitro, which can be initiated by the overexpression of a secretory form of the angiogenic fibroblast growth factor-1 (FGF-1) and mediated through the enzymatic activity of matrix metalloproteinase-1 (MMP-1). MMP-1 is a member of the MMP family with a propensity for degradation of interstitial type I collagen. We stably overexpressed a chimeric FGF-1 construct composed of the FGF-4 signal-peptide gene, linked in-frame to the FGF-1 coding frame gene (sp-FGF-1), in cultured postcapillary venular ECs. The presence of the biologically active form of FGF-1 was readily detected in the conditioned medium of ECs transfected with sp-FGF-1 construct as demonstrated by DNA synthesis assay. The sp-FGF-1-, but not the plasmid vector alone-transfected ECs, exhibited an altered morphology as demonstrated by their conversion from a classic cobblestone form to a fibroblastlike shape that featured prominent neuritelike extensions. Addition of the anti-FGF receptor 1 antibody (FGFR1 Ab) reverted the transformed phenotype of sp-FGF-1 transfectants. This suggests that the resulting phenotypic transformation in sp-FGF-1 transfectants requires an uninterrupted interaction between the FGF-1 ligand and its receptor. We studied migration of cells through matrices of either highly pure collagen I or reconstituted basement membrane (matrigel) and found that sp-FGF-1-transfected cells migrated two times and six times faster than the vector control transfectants in the respective matrices. We further demonstrated that the enhanced migration rate of sp-FGF-1-transfected EC coincided with the induction of their MMP-1 mRNA level and increased enzymatic activity. The enhanced migratory activity of sp-FGF-1 could be blocked with a selective inhibitor of MMP-1. These results suggest that the multipotent FGF-1 plays a key role in the early stages of angiogenesis, by mediating MMP-1 proteolytic activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0730-2312
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
78
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
487-99
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10861846-Animals, pubmed-meshheading:10861846-Blotting, Northern, pubmed-meshheading:10861846-Blotting, Western, pubmed-meshheading:10861846-Bromodeoxyuridine, pubmed-meshheading:10861846-Cattle, pubmed-meshheading:10861846-Cell Movement, pubmed-meshheading:10861846-Cells, Cultured, pubmed-meshheading:10861846-DNA, pubmed-meshheading:10861846-DNA Primers, pubmed-meshheading:10861846-Endothelium, Vascular, pubmed-meshheading:10861846-Fibroblast Growth Factor 1, pubmed-meshheading:10861846-Fibroblast Growth Factor 2, pubmed-meshheading:10861846-Gene Expression, pubmed-meshheading:10861846-Matrix Metalloproteinase 1, pubmed-meshheading:10861846-Plasmids, pubmed-meshheading:10861846-Protein Sorting Signals, pubmed-meshheading:10861846-RNA, Messenger, pubmed-meshheading:10861846-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:10861846-Transfection
pubmed:year
2000
pubmed:articleTitle
Overexpression of a secretory form of FGF-1 promotes MMP-1-mediated endothelial cell migration.
pubmed:affiliation
Department of Medical Physiology and Cardiovascular Institute, Texas A&M University, Health Science Center, College Station 77843, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't