Linked Life Data

14670838

Source:http://linkedlifedata.com/resource/pubmed/id/14670838

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-2-20
pubmed:abstractText
Thrombin and factor Xa (FXa) are agonists for G protein-coupled receptors (GPRCs) and may contribute to vascular lesion formation by stimulating proliferation of vascular smooth muscle cells (SMCs). Mitogenic signaling of GPCRs requires transactivation of receptor tyrosine kinases (RTKs). In rat SMCs, thrombin transactivates the epidermal growth factor receptor (EGFR) via a pathway that involves heparin-binding EGF-like growth factor (HB-EGF) as ligand for EGFR. The purpose of this study was to investigate in human SMCs the role of receptor transactivation in the mitogenic response to thrombin and FXa. Thrombin (10 nmol/L) and FXa (100 nmol/L) cause a 3.3- and 2.6-fold increase in DNA synthesis, respectively. In human SMCs, neither thrombin nor FXa causes EGFR phosphorylation, and blockade of EGFR kinase does not inhibit DNA synthesis. However, DNA synthesis and phosphorylation of fibroblast growth factor receptor-1 (FGFR-1) induced by thrombin or FXa are inhibited by antibodies neutralizing basic fibroblast growth factor (bFGF) or by heparin. Hirudin inhibits thrombin-, but not FXa-induced mitogenesis, indicating that FXa acts independently of thrombin. We further demonstrate by ELISA that upon thrombin and FXa stimulation, bFGF is released and binds to the extracellular matrix. Our data suggest that in human vascular SMCs, both thrombin and FXa rapidly release bFGF into the pericellular matrix. This is followed by transactivation of the FGFR-1 and increased proliferation. Heparin may inhibit the mitogenic effects of thrombin and FXa in human SMCs by preventing bFGF binding to FGFR-1.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
20
pubmed:volume
94
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
340-5
pubmed:dateRevised
2010-5-26
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Thrombin- and factor Xa-induced DNA synthesis is mediated by transactivation of fibroblast growth factor receptor-1 in human vascular smooth muscle cells.
pubmed:affiliation
Department of Surgery, University of Washington School of Medicine, Box 356410, 1959 NE Pacific St, Seattle, Wash 98195-6410, USA. brauch@u.washington.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't