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• W2004969894 abstract "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." @default.
• W2004969894 created "2016-06-24" @default.
• W2004969894 creator A5008791054 @default.
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• W2004969894 date "2008-06-01" @default.
• W2004969894 modified "2023-09-25" @default.
• W2004969894 title "Aldosterone and TGF-β₁synergistically increase PAI-1 and decrease matrix degradation in rat renal mesangial and fibroblast cells" @default.
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• W2004969894 doi "https://doi.org/10.1152/ajprenal.00017.2008" @default.
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