Pioglitazone attenuates TGF-β1-induction of fibronectin synthesis and its splicing variant in human mesangial cells via activation of peroxisome proliferator-activated receptor (PPAR)γ

The peroxisome proliferator-activated receptor (PPAR)gamma is expressed not only in adipose tissue but also in macrophages/monocytes and plays important roles in acute/chronic inflammation. Transforming growth factor (TGF)-beta is a common pathogenic indicator of sclerosis because it induces the accumulation of extracellular matrix (ECM) in the glomerular mesangium of the kidney. Among components of the ECM. fibronectin (FN) is an acute reactant in inflammation. and isoforms of it produced by splicing of gene variants appear during abnormal conditions such as wound healing. In this study, we examined the effects of pioglitazone, a PPAR gamma agonist, on TGF-beta(1)-induced FN synthesis in cultured mesangial cells using RT-PCR and Western blot analysis. We also analyzed its splicing variant, extra domain (ED) A, containing FN (EDA(+) FN). TGF-beta(1) enhanced the production of both FN and EDA(+) FN and down-regulated PPAR gamma expression. Pioglitazone reversed both these effects of TGF-beta(1), These findings suggest that PPAR gamma activation by pioglitazone may affect the TGF-beta(1)-induced FN accumulation observed in the glomerular mesangium in cases of glomerulosclerosis, although further in vivo experiments are needed to evaluate this influence. (c) 2005 International Federation for Cell Biology. Published by Elsevier Ltd, All rights reserved.