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.
The First Clinical Medical College of Jinan University, Guangzhou, 510630 Guangdong Province China.|Department of Intensive Care Unit, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021 China.
Shulin
S
Xiang
Department of Central Laboratory, Youjiang Medical University for Nationalities, Baise, 533000 Guangxi Zhuang Autonomous Region China.
Yi
Y
Zeng
Department of Intensive Care Unit, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021 China.
Bin
B
Xiong
Department of Digestive Medicine, Youjiang Medical University for Nationalities, Baise, 533000 Guangxi Zhuang Autonomous Region China.
Yueqiu
Y
Qin
The First Clinical Medical College of Jinan University, Guangzhou, 510630 Guangdong Province China.|Department of Respiratory Medicine, Youjiang Medical University for Nationalities, Baise, 533000 Guangxi Zhuang Autonomous Region China.
Xia
X
Huang
The First Clinical Medical College of Jinan University, Guangzhou, 510630 Guangdong Province China.|Department of Respiratory Medicine, Youjiang Medical University for Nationalities, Baise, 533000 Guangxi Zhuang Autonomous Region China.
Yujie
Y
Jiang
Department of Respiratory Medicine, Youjiang Medical University for Nationalities, Baise, 533000 Guangxi Zhuang Autonomous Region China.
Weigui
W
Luo
Department of Surgery and Cancer, Imperial College London, Chelsea and Westminster Hospital, London, SW10 9NH UK.
Suren R
SR
Sooranna
Department of Intensive Care Medicine, Youjiang Medical University for Nationalities, Baise, 533000 Guangxi Zhuang Autonomous Region China.
Liao
L
Pinhu
Endothelin-1; PPAR-γ; TGF-β1