Linked Life Data

18602101

Source:http://linkedlifedata.com/resource/pubmed/id/18602101

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2008-7-25
pubmed:abstractText
Targeting of transforming growth factor beta (TGF-beta) to the extracellular matrix (ECM) by latent TGF-beta binding proteins (LTBPs) regulates the availability of TGF-beta for interactions with endothelial cells during their quiescence and activation. However, the mechanisms which release TGF-beta complexes from the ECM need elucidation. We find here that morphological activation of endothelial cells by phorbol 12-myristate 13-acetate (PMA) resulted in membrane-type 1 matrix metalloproteinase (MT1-MMP) -mediated solubilization of latent TGF-beta complexes from the ECM by proteolytic processing of LTBP-1. These processes required the activities of PKC and ERK1/2 signaling pathways and were coupled with markedly increased MT1-MMP expression. The functional role of MT1-MMP in LTBP-1 release was demonstrated by gene silencing using lentiviral short-hairpin RNA as well as by the inhibition with tissue inhibitors of metalloproteinases, TIMP-2 and TIMP-3. Negligible effects of TIMP-1 and uPA/plasmin system inhibitors indicated that secreted MMPs or uPA/plasmin system did not contribute to the release of LTBP-1. Current results identify MT1-MMP-mediated proteolytic processing of ECM-bound LTBP-1 as a mechanism to release latent TGF-beta from the subendothelial matrix.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1090-2422
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
314
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2501-14
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18602101-Cell Shape, pubmed-meshheading:18602101-Cells, Cultured, pubmed-meshheading:18602101-Endothelial Cells, pubmed-meshheading:18602101-Extracellular Matrix, pubmed-meshheading:18602101-Gene Expression Regulation, Enzymologic, pubmed-meshheading:18602101-Humans, pubmed-meshheading:18602101-Latent TGF-beta Binding Proteins, pubmed-meshheading:18602101-Matrix Metalloproteinase 14, pubmed-meshheading:18602101-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:18602101-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:18602101-Protein Kinase C, pubmed-meshheading:18602101-Protein Processing, Post-Translational, pubmed-meshheading:18602101-RNA, Small Interfering, pubmed-meshheading:18602101-Signal Transduction, pubmed-meshheading:18602101-Transforming Growth Factor beta1
pubmed:year
2008
pubmed:articleTitle
MT1-MMP releases latent TGF-beta1 from endothelial cell extracellular matrix via proteolytic processing of LTBP-1.
pubmed:affiliation
Departments of Pathology and Virology, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't