Transforming growth factor beta 1 induced endothelin-1 release is peroxisome proliferator-activated receptor gamma dependent in A549 cells

Background: endothelin-1 (et-1) is involved in pulmonary vascular remodeling. the aim of this study was to investigate the biochemical interactions between ppar-γ,tgf-β1 and et-1 in vitro. methods: a549 cells were pre-treated with s2505 (10 μm),s2871 (10 μm) with/without sb203580 (10 μm) for 60 min following 2 h treatment with 10 ng/ml tgf-β1. a549 cells were also transfected with positive or negative ppar-γ plasmids for comparison. rt-pcr,elisa,western blotting and confocal laser scanning microscopy (clsm) were used to measure the relevant expression of mrna,protein,mediators of pathways and nuclear factor translocation. results: sb203580 inhibited tgf-β1 induced et-1 expression in a549 cells. s2871 decreased ppar-γ mrna and increase tgf-β1-induced et-1 expression. s2871 increased phosphorylation of p38 mapk and smad2. cells transfected with ppar-γ negative plasmid increased tgf-β1 induced et-1 expression,and increased the expression of phospho-p38 mapk and phospho-smad2. s2505 increased ppar-γ mrna expression,suppressed the increased tgf-β1-induced expression of et-1. s2505 inhibited tgf-β1 induced phosphorylation of p38 mapk and smad2,also the nuclear translocation of smad2. cells transfected with ppar-γ positive plasmid reduced tgf-β1-induced et-1 expression,and inhibited the expression of phospho-p38 mapk and phospho-smad2. conclusions: tgf-β1 induced release of endothelin-1 is ppar-γ dependent in cultured a549 cells. © 2016 the author(s).