Transforming growth factor beta 1 induced endothelin-1 release is peroxisome proliferator-activated receptor gamma dependent in A549 cells.
Transforming growth factor beta 1 induced endothelin-1 release is peroxisome proliferator-activated receptor gamma dependent in A549 cells.
复制标题
A549 细胞中转化生长因子 β 1 诱导的内皮素 1 释放是过氧化物酶体增殖物激活受体 γ 依赖性的
DOI：
10.1186/s12950-016-0128-1
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Pinhu L
中科院分区：
文献类型：
--
作者：
Xiang S;Zeng Y;Xiong B;Qin Y;Huang X;Jiang Y;Luo W;Sooranna SR;Pinhu L
内皮素-1(ET-1)参与肺血管重构。本研究的目的是探讨PPAR-γ、转化生长因子-β-1和ET-1在体外的生化相互作用。分别用S2505(10μM)、S2871(10μM)和SB203580(10μM)处理A549细胞60 h，再用10 ng/mLTf-β-1处理2 h。同时将阳性和阴性pPAR-γ载体分别导入A549细胞作为对照。采用逆转录聚合酶链式反应、酶联免疫吸附试验、免疫印迹和激光共聚焦扫描显微镜(CLSM)检测相关基因、蛋白、信号转导途径和核因子转位的表达。SB203580抑制转化生长因子-β-1诱导的A549细胞ET-1的表达。S2871降低PPAR-γ基因表达，增加β-1诱导的ET-1表达。S2871使p38MAPK和Smad2的磷酸化水平升高。PPAR-γ阴性表达载体可增加转化生长因子-β-1诱导的ET-1的表达，增加p38MAPK和Smad2的表达。S2505上调PPAR-γ基因表达，抑制转化生长因子-β1诱导的ET-1表达增加。S2505抑制转化生长因子-β1诱导的p38MAPK和Smad2的磷酸化，以及Smad2的核转位。PPAR-γ阳性表达载体可降低转化生长因子-β1诱导的ET-1的表达，抑制p38MAPK和Smad2的表达。转化生长因子-β-1诱导A549细胞释放内皮素-1依赖于PPAR-γ。
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. 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. 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. TGF-β1 induced release of endothelin-1 is PPAR-γ dependent in cultured A549 cells.