Impact of PGE1 on cyclosporine A induced up-regulation of TGF-β1, its receptors, and related matrix production in cultured mesangial cells

Transforming growth factor-beta1 (TGF-beta1) plays a major role in cyclosporine A (CsA) induced glomerulosclerosis. We have recently shown that CsA up-regulates the expression of TGF-beta1 and its receptors type I (TbetaR-I) and type 11 (TbetaR-II) in rat mesangial cells (MCs). Prostaglandins of the E series (PGEs) are known to exert substantial anti-fibrotic effects. Here, we assessed the effect of PGE(1) on CsA induced up-regulation of TGF-beta1, TbetaR-I, TbetaR-II and related matrix production in MCs. Co-incubation with PGE(1) reduced CsA induced up-regulation of TGF-beta1 and TbetaR-II at the mRNA and protein level. Alike, PGE(1) reduced TbetaR-I protein expression, which is posttranscriptionally up-regulated by CsA. Whereas a low PGE1 concentration decreased CsA induced production of fibronectin (FN) and plasminogen activator inhibitor type-1 (PAI-1), a higher PGE(1) concentration did not change FN production, but further increased PAI-1 production. In vivo studies will show, whether treatment with PGE(1) analogues will be useful in preventing CsA induced glomerulosclerosis. (C) 2003 Elsevier Ltd. All rights reserved.