Key Points
- To investigate whether aldosterone promotes renal fibrosis via TGF-β1-mediated induction of PAI-1 and to determine if aldosterone and TGF-β1 act synergistically to suppress extracellular matrix degradation.
- Treated rat mesangial cells (MCs) and normal rat kidney fibroblasts (NRK-49F) with aldosterone, TGF-β1, the mineralocorticoid receptor antagonist spironolactone, or TGF-β neutralizing antibodies.
- Measured PAI-1 mRNA and protein expression across treatment conditions.
- Assessed extracellular matrix degradation by newly plated MCs and NRK-49F cells through quantifying the release of tritium from 3H-labeled mesangial cell matrix into culture media.
- Aldosterone markedly increased PAI-1 mRNA and protein in both cell lines; this effect was completely prevented by spironolactone and partially inhibited by TGF-β neutralizing antibodies.
- Aldosterone or TGF-β1 alone decreased matrix degradation by 39% and 49% in MCs, and by 21% and 23% in NRK-49F cells, respectively.
- Combined treatment with aldosterone and TGF-β1 produced supra-additive increases in PAI-1 and further reduced matrix degradation by 93% in MCs and 61% in NRK-49F cells.
Structured PICO
PPopulationRat mesangial cells (MCs) and fibroblast cells [normal rat kidney (NRK)-49F]
IInterventionAldosterone and TGF-beta1 (alone and in combination)
CComparatorUntreated cells or single compound treatment
OOutcomePAI-1 mRNA and protein levels, and extracellular matrix (ECM) degradationsurrogate
Aldosterone and TGF-beta1 act synergistically to increase PAI-1 production and decrease extracellular matrix degradation in rat renal cells, highlighting a mechanism for RAAS-induced fibrosis.