血管紧张素转换酶抑制剂对人肺成纤维细胞的促纤维化作用。
Profibrosing effect of angiotensin converting enzyme inhibitors in human lung fibroblasts.
作者信息
Díaz-Piña Gabriela, Montes Eduardo, Checa Marco, Becerril Carina, García de Alba Carolina, Vega Anita, Páramo Ignacio, Ordoñez-Razo Rosa, Ruiz Victor
机构信息
Departamento de Biología Molecular, Instituto Nacional de Enfermedades Respiratorias,"Ismael Cosío Villegas", Calz. Tlalpan 4502, Col. Sección XVI, 14080, D.F., Mexico.
出版信息
Lung. 2015 Apr;193(2):199-202. doi: 10.1007/s00408-015-9688-8. Epub 2015 Feb 6.
OBJECTIVE
The objective of this study is to determine the effect of two angiotensin-converting enzyme inhibitors (ACEi) (Enalapril and Captopril), an angiotensin-II receptor inhibitor (Losartan) and a renin inhibitor (Aliskiren) on renin, TGF-β1 and collagen expressions in human lung fibroblast cultures through real-time PCR and ELISA.
MATERIALS AND METHODS
Normal commercial fibroblasts (CCD25) were exposed to 10(-6) M of enalapril, captopril, losartan, or aliskiren for 6 h. Subsequently, media were recovered and proteins were concentrated; RNA was extracted from the cells. Real time-PCR and ELISA were performed.
RESULTS
ACEi and losartan-stimulated fibroblasts showed an increase in the expression of TGF-β1, Collagen-Iα1 (Col-Iα1), and renin (except losartan) vs PolR2A (p < 0.05), and upregulation of TGF-β1 protein (p < 0.01), except with aliskiren.
CONCLUSION
Results show that ACEis and losartan could play a profibrosing role by inducing the overexpression of molecules such TGF-β1 and Collagen.
目的
本研究旨在通过实时定量聚合酶链反应（PCR）和酶联免疫吸附测定（ELISA），确定两种血管紧张素转换酶抑制剂（ACEi）（依那普利和卡托普利）、一种血管紧张素II受体抑制剂（氯沙坦）和一种肾素抑制剂（阿利吉仑）对人肺成纤维细胞培养物中肾素、转化生长因子-β1（TGF-β1）和胶原蛋白表达的影响。
材料与方法
将正常商业成纤维细胞（CCD25）暴露于10⁻⁶ M的依那普利、卡托普利、氯沙坦或阿利吉仑中6小时。随后，收集培养基并浓缩蛋白质；从细胞中提取RNA。进行实时定量PCR和ELISA检测。
结果
与PolR2A相比，ACEi和氯沙坦刺激的成纤维细胞中TGF-β1、I型胶原蛋白α1（Col-Iα1）和肾素（氯沙坦除外）的表达增加（p < 0.05），TGF-β1蛋白上调（p < 0.01），阿利吉仑除外。
结论
结果表明，ACEi和氯沙坦可能通过诱导TGF-β1和胶原蛋白等分子的过度表达发挥促纤维化作用。
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