Linked Life Data

18367662

Source:http://linkedlifedata.com/resource/pubmed/id/18367662

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-6-6
pubmed:abstractText
Aldosterone is thought to modulate renal fibrosis, in part, through increasing plasminogen activator inhibitor type 1 (PAI-1), a major inhibitor of ECM degradation. The present study investigated aldosterone effects on PAI-1 and transforming growth factor (TGF)-beta(1) and asked whether PAI-1 effects were TGF-beta mediated and whether aldosterone and TGF-beta(1) acted synergistically to increase PAI-1 and decrease ECM degradation. Rat mesangial cells (MCs) and fibroblast cells [normal rat kidney (NRK)-49F] were used. (3)H-labeled ECM was produced by MCs. The effect of aldosterone and TGF-beta on ECM degradation by newly plated MCs or NRK-49F was measured by the release of (3)H into medium. Aldosterone markedly increased PAI-1 mRNA and protein in both cell types, increases completely blocked by spironolactone and partially blocked by TGF-beta neutralizing antibody. Adding both aldosterone and TGF-beta(1) produced PAI-1 mRNA and protein increases higher than the sum of increases seen with either compound alone. Aldosterone or TGF-beta(1) alone inhibited matrix degradation by 39 and 49% in MCs and 21 and 23% in NRK-49F, respectively. When both compounds were added, matrix degradation was further decreased by 93% in MCs and 61% in NRK-49F. The results indicate that aldosterone-induced PAI-1 increases are partially mediated by TGF-beta(1) and lead to decreased ECM degradation. While aldosterone alone induced TGF-beta(1) weakly, aldosterone and TGF-beta(1) added together produced dramatic synergistic effects on PAI-1 production and subsequent ECM accumulation. Thus the elevated aldosterone induced by renin-angiotensin-aldosterone system activation may amplify renin-angiotensin-aldosterone system profibrotic actions.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1931-857X
pubmed:author
pubmed:issnType
Print
pubmed:volume
294
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
F1287-95
pubmed:dateRevised
2011-4-28
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Aldosterone and TGF-beta1 synergistically increase PAI-1 and decrease matrix degradation in rat renal mesangial and fibroblast cells.
pubmed:affiliation
Fibrosis Research Laboratory, Division of Nephrology, University of Utah School of Medicine, Salt Lake City, UT 84108, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural