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

Autor: Kunimi Maeda, Yasuhiko Tomino, Satoshi Horikoshi, Atsuko Maeda, Toshinao Tsuge, Tomohito Gohda
Rok vydání: 2005
Předmět:
Zdroj: Cell Biology International. 29:422-428
ISSN: 1065-6995
Popis: The peroxisome proliferator-activated receptor (PPAR)γ is expressed not only in adipose tissue but also in macrophages/monocytes and plays important roles in acute/chronic inflammation. Transforming growth factor (TGF)-β 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 PPARγ agonist, on TGF-β1-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-β1 enhanced the production of both FN and EDA+ FN and down-regulated PPARγ expression. Pioglitazone reversed both these effects of TGF-β1. These findings suggest that PPARγ activation by pioglitazone may affect the TGF-β1-induced FN accumulation observed in the glomerular mesangium in cases of glomerulosclerosis, although further in vivo experiments are needed to evaluate this inference.
Databáze: OpenAIRE
Externí odkaz: