β-adrenergic receptor-dependent alterations in murine cardiac transcript expression are differentially regulated by gefitinib in vivo.
β-adrenergic receptor-dependent alterations in murine cardiac transcript expression are differentially regulated by gefitinib in vivo.
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DOI：
10.1371/journal.pone.0099195
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Tilley DG
中科院分区：
文献类型：
--
作者：
Talarico JA;Carter RL;Grisanti LA;Yu JE;Repas AA;Tilley DG
在小鼠心力衰竭模型中，β-肾上腺素能受体（βAR）介导的表皮生长因子受体（EGFR）的转激活已被证明可以促进心脏保护，我们最近发现，这种机制部分通过调节分离的大鼠新生心肌细胞的凋亡转录物表达来提高细胞存活率。因此，我们假设这一过程可以调节心脏转录物在体内的表达。为了全面评估急性βAR依赖性EGFR转激活对心脏转录的影响，我们对C57BL/6小鼠的心脏进行了全转录组分析，在存在或不存在EGFR拮抗剂吉非替尼的情况下，腹腔注射βAR激动剂异丙肾上腺素1小时。对每个治疗组的总心脏RNA进行转录组分析，揭示了每种治疗调节的大量转录本。吉非替尼单独显著改变了405个转录本的表达，而异丙肾上腺素单独或联合吉非替尼分别显著改变了493个和698个不同的转录本。进一步的统计分析证实了473个转录本的异丙肾上腺素调控被吉非替尼显著改变（异丙肾上腺素诱导的上调/下调被吉非替尼拮抗/促进），其中包括一些已知参与许多过程的调控，包括细胞死亡和存活。因此，体内β ar依赖性心脏转录物表达的调节可以通过EGFR拮抗剂吉非替尼进行调节。
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.
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影响因子：
3.9
作者：
Chen, Hao;Ma, Ning;Xu, Zhiwei
通讯作者：
Xu, Zhiwei
影响因子：
20.1
作者：
Gonzalez-Quesada C;Cavalera M;Biernacka A;Kong P;Lee DW;Saxena A;Frunza O;Dobaczewski M;Shinde A;Frangogiannis NG
通讯作者：
Frangogiannis NG
DOI：
10.1124/jpet.107.133975
发表时间：
2008-03-01
影响因子：
3.5
作者：
Errami, Mounir;Galindo, Cristi L.;Garner, Harold R.
通讯作者：
Garner, Harold R.
影响因子：
20.1
作者：
Matkovich, Scot J.;Zhang, Yan;Dorn, Gerald W., II
通讯作者：
Dorn, Gerald W., II
影响因子：
15.9
作者：
Ieda, M;Fukuda, K;Ogawa, S
通讯作者：
Ogawa, S