Center for Genomic Medicine, Bioinformatics, Medical University of South Carolina, Charleston, SC, USA.
Faculty of Medicine, Health & Life Sciences, School of Biological Sciences, Institute for Global Food Security (IGFS), Belfast, Northern Ireland, UK.
Pharmacogenomics. 2019 Nov;20(16):1125-1141. doi: 10.2217/pgs-2019-0077.
The objective was to determine via high-throughput RNA sequencing the temporal effects of rosiglitazone (Avandia) on the neonatal rat ventricular myocyte transcriptome. Neonatal rat ventricular myocytes (NRVMs) were exposed to rosiglitazone . Meta analyses utilized temporal comparisons of 0.5 h control versus 0.5 h treatment, 0.5 h treatment versus 24 h treatment and 24 h treatment versus 48 h treatment. Time dependent responses were observed. At 0.5 h, the PI3K-AKT signaling pathway was impacted. At 24 h endoplasmic reticulum activity and protein degradation were altered. At 48 h, oxytocin signaling was perturbed. The effects of rosiglitazone occured early and increased in magnitude over time. A protective molecular response was triggered at 24 h and maintained until 48 h. In parallel, a response that can cause cardiac damage was activated. Our findings suggest that rosiglitazone has deleterious effects.
目的是通过高通量 RNA 测序确定罗格列酮（文迪雅）对新生大鼠心室肌细胞转录组的时间效应。将新生大鼠心室肌细胞（NRVMs）暴露于罗格列酮中。荟萃分析利用 0.5 h 对照与 0.5 h 处理、0.5 h 处理与 24 h 处理和 24 h 处理与 48 h 处理的时间比较。观察到时间依赖性反应。在 0.5 h 时，PI3K-AKT 信号通路受到影响。在 24 h 时，内质网活性和蛋白质降解发生改变。在 48 h 时，催产素信号受到干扰。罗格列酮的作用发生得较早，随着时间的推移，其作用强度逐渐增加。在 24 h 时触发了一种保护分子反应，并持续到 48 h。与此同时，激活了一种可能导致心脏损伤的反应。我们的研究结果表明，罗格列酮具有有害作用。
