Linked Life Data

10623891

Source:http://linkedlifedata.com/resource/pubmed/id/10623891

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-1-27
pubmed:abstractText
Induced expression of plasminogen activator inhibitor type-1 (PAI-1), a major negative regulator of pericellular plasmin generation, accompanies wound repair in vitro and in vivo. Since transcriptional control of the PAI-1 gene is superimposed on a growth state-dependent program of cell activation (Kutz et al., 1997, J Cell Physiol 170:8-18), it was important to define potentially functional relationships between PAI-1 synthesis and subpopulations of cells that emerge during the process of injury repair in T2 renal epithelial cells. Specific cohorts of migratory and proliferating cells induced in response to monolayer trauma were spatially as well as temporally distinct. Migrating cells did not divide in the initial 12 to 20 h postinjury. After 24 h, S-phase cells were generally restricted to a region 1 to 2 mm from, and parallel to, the wound edge. Proliferation of wound bed cells occurred subsequent to wound closure, whereas the distal contact-inhibited monolayer remained generally quiescent. Hydroxyurea blockade indicated, however, that proliferation (most likely of cells immediately behind the motile "tongue") was necessary for maintenance of cell-to-cell cohesiveness in the advancing front, although the ability to migrate was independent of proliferation. PAI-1 mRNA expression was rapidly up-regulated in response to wounding with inductive kinetics approximating that of serum-stimulated cultures. Differential harvesting of T2 cell subpopulations, based on proximity to the injury site, prior to Northern assessments of PAI-1 mRNA abundance indicated that PAI-1 transcripts were restricted to cells immediately bordering the wound or actively migrating and not expressed by cells in the distal contact-inhibited monolayer regions. Such cell location-specific distribution of PAI-1-producing cells was confirmed by immunocytochemistry. PAI-1 synthesis in cells that locomoted into the wound field continued until injury closure. Down-regulation of PAI-1 synthesis and matrix deposition in renal epithelial cells, stably transfected with a PAI-1 antisense expression vector, significantly impaired wound closure. Transfection of the wound repair-deficient R/A epithelial line with a sense PAI-1 expression construct restored both approximately normal levels of PAI-1 synthesis and repair ability. These data indicate that PAI-1 induction is an early event in creation of the wound-activated phenotype and appears to participate in the regulation of renal epithelial cell motility during in vitro injury resolution.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9541
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
182
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
269-80
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
PAI-1 gene expression is regionally induced in wounded epithelial cell monolayers and required for injury repair.
pubmed:affiliation
Cell & Molecular Biology Program, Albany Medical College, Albany, NY 12208, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.