Endothelin-1 enhances β2-adrenoceptor gene transcription in human lung fibroblasts

[摘要] Aims: The present study aimed to explore possible effects of endothelin-1 (ET-1) on beta 2-adrenoceptor gene transcription in human lung fibroblasts. Main methods: MRC-5 human lung fibroblasts were cultured in absence or presence of test substances, followed by beta 2-adrenoceptor mRNA determination by quantitative real time PCR. Key findings: ET-1 caused a marked and rapid in onset (1 hr) increase in beta 2-adrenoceptor mRNA, an effect additive to that of short time (1 hr) exposure to the beta(2)-adrenoceptor agonist olodaterol. The stimulatory effect of ET-1 on beta 2-adrenoceptor mRNA was prevented by the non-selective ET-A/ET-B receptor antagonist bosentan, indicating that it was mediated via specific ET receptors. In the presence of actinomycin D the effect of ET-1 was prevented indicating that ET-1 acts via increased transcription of the beta 2-adrenoceptor gene. ET-1-induced up-regulation off beta 2-adrenoceptor mRNA was also seen in the presence of cycloheximide excluding indirect effects via up-regulation of other regulatory proteins. Conclusions: ET-1 can up-regulate beta-adrenoceptor gene transcription in human lung fibroblasts. (c) 2012 Elsevier Inc. All rights reserved.

[发布日期] 2012-10-15

[效力级别]  Proceedings Paper

[关键词] Endothelin-1;beta 2-adrenoceptor expression;Lung fibroblasts