罗格列酮暴露的新生大鼠心肌细胞中的发育和细胞外基质重塑过程。
Developmental and extracellular matrix-remodeling processes in rosiglitazone-exposed neonatal rat cardiomyocytes.
机构信息
Department of Biology, San Diego State University, CA, USA.
出版信息
Pharmacogenomics. 2014 Apr;15(6):759-74. doi: 10.2217/pgs.14.39.
OBJECTIVE
The objective of this study was to investigate the effects of rosiglitazone (Avandia(®)) on gene expression in neonatal rat ventricular myocytes.
MATERIALS & METHODS: Myocytes were exposed to rosiglitazone ex vivo. The two factors examined in the experiment were drug exposure (rosiglitazone and dimethyl sulfoxide vs dimethyl sulfoxide), and length of exposure to drug (½ h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 18 h, 24 h, 36 h and 48 h).
RESULTS
Transcripts that were consistently expressed in response to the drug were identified. Cardiovascular system development, extracellular matrix and immune response are represented prominently among the significantly modified gene ontology terms.
CONCLUSION
Hmgcs2, Angptl4, Cpt1a, Cyp1b1, Ech1 and Nqo1 mRNAs were strongly upregulated in cells exposed to rosiglitazone. Enrichment of transcripts involved in cardiac muscle cell differentiation and the extracellular matrix provides a panel of biomarkers for further analysis in the context of adverse cardiac outcomes in humans. Original submitted 15 November 2013; Revision submitted 14 February 2014.
目的
本研究旨在探讨罗格列酮（文迪雅(®)）对新生大鼠心室肌细胞基因表达的影响。
材料与方法
将心肌细胞进行离体暴露实验。实验中检查了两个因素，即药物暴露（罗格列酮和二甲基亚砜与二甲基亚砜）和药物暴露时间（½ h、1 h、2 h、4 h、6 h、8 h、12 h、18 h、24 h、36 h 和 48 h）。
结果
鉴定出对药物有一致反应的转录本。心血管系统发育、细胞外基质和免疫反应在显著改变的基因本体术语中表现突出。
结论
暴露于罗格列酮的细胞中 Hmgcs2、Angptl4、Cpt1a、Cyp1b1、Ech1 和 Nqo1 mRNA 强烈上调。涉及心肌细胞分化和细胞外基质的转录本的富集为进一步分析人类不良心脏结局提供了一组生物标志物。原始提交日期为 2013 年 11 月 15 日；修订后提交日期为 2014 年 2 月 14 日。
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