Data from: β-adrenergic receptor-dependent alterations in murine cardiac transcript expression are differentially regulated by gefitinib in vivo

β-adrenergic receptor (βAR)-mediated transactivation of epidermal growth factor receptor (EGFR) has been shown to promote cardioprotection in a mouse model of heart failure and we recently showed that this mechanism leads to enhanced cell survival in part via regulation of apoptotic transcript expression in isolated primary rat neonatal cardiomyocytes. Thus, we hypothesized that this process could regulate cardiac transcript expression in vivo. To comprehensively assess cardiac transcript alterations in response to acute βAR-dependent EGFR transactivation, we performed whole transcriptome analysis of hearts from C57BL/6 mice given i.p. injections of the βAR agonist isoproterenol in the presence or absence of the EGFR antagonist gefitinib for 1 hour. Total cardiac RNA from each treatment group underwent transcriptome analysis, revealing a substantial number of transcripts regulated by each treatment. Gefitinib alone significantly altered the expression of 405 transcripts, while isoproterenol either alone or in conjunction with gefitinib significantly altered 493 and 698 distinct transcripts, respectively. Further statistical analysis was performed, confirming 473 transcripts whose regulation by isoproterenol were significantly altered by gefitinib (isoproterenol-induced up/downregulation antagonized/promoted by gefinitib), including several known to be involved in the regulation of numerous processes including cell death and survival. Thus, βAR-dependent regulation of cardiac transcript expression in vivo can be modulated by the EGFR antagonist gefitinib.

β肾上腺素能受体（β-adrenergic receptor, βAR）介导的表皮生长因子受体（epidermal growth factor receptor, EGFR）反式激活，已被证实可在心力衰竭小鼠模型中发挥心脏保护作用；本团队近期研究发现，该机制可通过调控原代新生大鼠心肌细胞的凋亡相关转录本表达，部分增强细胞存活能力。据此，本研究提出假说：该过程可在体内调控心脏转录组的表达。为全面评估急性βAR依赖型EGFR反式激活所引发的心脏转录组改变，研究人员对C57BL/6小鼠的心脏开展了全转录组分析：小鼠经腹腔注射（i.p.）βAR激动剂异丙肾上腺素（isoproterenol），同时联合或不联合EGFR拮抗剂吉非替尼（gefitinib），处理时长为1小时。各处理组的心脏总RNA均进行转录组分析，结果显示各处理组均调控了大量转录本。单独使用吉非替尼可显著改变405个转录本的表达水平；而单独使用异丙肾上腺素，以及异丙肾上腺素联合吉非替尼处理组，分别显著改变了493个和698个独特转录本的表达。进一步的统计学分析证实，共有473个转录本的异丙肾上腺素诱导表达调控可被吉非替尼显著改变（即吉非替尼拮抗或促进异丙肾上腺素诱导的转录本上调/下调），其中包含多个已知参与调控细胞死亡与存活等多种生物学过程的转录本。综上，体内βAR依赖型心脏转录组表达调控可被EGFR拮抗剂吉非替尼所调控。