PPAR-gamma Agonist Suppresses 11beta-hydroxysteroid Dehydrogenase Type 1 Expression and Alleviates Glucocorticoid-induced ACE Gene Expression in Cardiac Fibroblasts

Abstract

Purpose: We previously reported corticosteroids augment the gene expression of angiotensin converting enzyme (ACE) through glucocorticoid receptor (GR) in cultured cardiac fibroblasts (CF). However, GR-active corticosterone is unable to enter the cells because of its binding to carrier protein in the serum, whereas GR-inactive 11-dehydroxycorticosterone (11-DHB) enter the cells and is converted to corticosterone by 11beta-hydroxysteroid dehydrogenase (11beta-HSD1) to stimulate GR. Here, we tested the hypothesis that 11beta-HSD1 is implicated in the activation of GR in CF and determined the effect of PPAR-gamma agonist on the above action.