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Transforming growth factor beta 1 induced endothelin-1 release is peroxisome
proliferator-activated receptor gamma dependent in A549 cells
#MMPMID27293383
Xiang S
; Zeng Y
; Xiong B
; Qin Y
; Huang X
; Jiang Y
; Luo W
; Sooranna SR
; Pinhu L
J Inflamm (Lond)
2016[]; 13
(?): 19
PMID27293383
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BACKGROUND: Endothelin-1 (ET-1) is involved in pulmonary vascular remodeling. The
aim of this study was to investigate the biochemical interactions between PPAR-?,
TGF-?1 and ET-1 in vitro. METHODS: A549 cells were pre-treated with S2505
(10 ?M), S2871 (10 ?M) with/without SB203580 (10 ?M) for 60 min following 2 h
treatment with 10 ng/mL TGF-?1. A549 cells were also transfected with positive or
negative PPAR-? 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-?1 induced ET-1 expression in A549
cells. S2871 decreased PPAR-? mRNA and increase TGF-?1-induced ET-1 expression.
S2871 increased phosphorylation of p38 MAPK and Smad2. Cells transfected with
PPAR-? negative plasmid increased TGF-?1 induced ET-1 expression, and increased
the expression of phospho-p38 MAPK and phospho-Smad2. S2505 increased PPAR-? mRNA
expression, suppressed the increased TGF-?1-induced expression of ET-1. S2505
inhibited TGF-?1 induced phosphorylation of p38 MAPK and Smad2, also the nuclear
translocation of Smad2. Cells transfected with PPAR-? positive plasmid reduced
TGF-?1-induced ET-1 expression, and inhibited the expression of phospho-p38 MAPK
and phospho-Smad2. CONCLUSIONS: TGF-?1 induced release of endothelin-1 is PPAR-?
dependent in cultured A549 cells.
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