过氧化物酶体增殖物激活受体γ激动剂对二氧化硅致成纤维细胞纤维连接蛋白表达的影响(英文)

Effects of peroxisome proliferator-activated receptor gamma agonists on fibronectin expression after SiO_2 stimulation

背景：过氧化物酶体增殖物激活受体γ激动剂对转化生长因子β1致矽肺肺间质纤维化作用的影响及机制尚不明确,罕见报道。目的：观察过氧化物酶体增殖物激活受体γ激动剂对转化生长因子β1致矽肺肺纤维化作用的影响。方法：200mg/LSiO2刺激SD大鼠肺泡巨噬细胞培养上清液作用于中国仓鼠肺成纤维细胞株（CHL）建立矽肺纤维化的体外细胞模型。RT-PCR检测过氧化物酶体增殖物激活受体γ配体15d-PGJ2及其激动剂曲格列酮和齐格列酮对转化生长因子β1诱导CHL的纤维连接蛋白mRNA表达的影响。利用Western印迹技术观察过氧化物酶体增殖物激活受体γ激动剂对转化生长因子β1诱导CHL的纤维连接蛋白表达的影响。结果与结论：①转化生长因子β1mRNA表达呈一定范围内的剂量（0~5μg/L）和时间（0~24h）依赖效应。②过氧化物酶体增殖物激活受体γ配体及激动剂降低了纤维连接蛋白mRNA和蛋白的表达。结果提示过氧化物酶体增殖物激活受体γ激动剂可以抑制转化生长因子β1诱导的SiO2致肺成纤维细胞纤维连接蛋白合成,具有抗SiO2所致肺间质纤维化的潜在作用。

BACKGROUND：The effect and mechanism of peroxisome proliferator-activated receptor gamma（PPARγ）agonists on transforming growth factor（TGF）-β1-induced fibrotic responses in lung fibroblasts remain unclear,and seldom reported.OBJECTIVE：To study the effects of PPARγ agonists on TGF-β1-induced fibrotic responses in lung fibroblasts,so as to investigate its effects in preventing pulmonary interstitial fibrosis of silicosis.METHODS：The pulmonary alveolar macrophage was prepared with 200 mg/L SiO2 and the supernatants were got.Chinese hamster lung fibroblasts were incubated with the prepared supernatants.Then a cellular model in vitro for studying pulmonary fibrosis induced by SiO2 was developed.Chinese hamster lung fibroblasts were cultured to observe the effects of the PPARγ ligand（15 d-PGJ2）and its agonists（troglitazone and ciglitazone）on the expression of TGF-β1-induced fibronectin.RT-PCR was used to detect the mRNA expression of fibronectin and Western blotting was used to detect the protein expression of fibronectin.RESULTS AND CONCLUSION：（1） The expression of TGF-β1 mRNA showed an effect in a dose-（0-5 μg/L）and time-（0-24 hours）dependent manner.（2）PPARγ ligands and agonists reduced the mRNA and protein expressions of fibronectin.Results suggested that PPARγ agonists can inhibit TGF-β1-induced fibronectin synthesis after stimulation by SiO2 and may play a potential role in preventing pulmonary interstitial fibrosis.