Premium
Acute cardiac gene expression changes mediated through beta‐AR‐mediated transactivation of EGFR in vivo
Author(s) -
Carter Rhonda L,
Talarico Jennfer A,
Grisanti Laurel A,
Yu Justine,
Tilley Douglas G
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.652.18
Subject(s) - transactivation , downregulation and upregulation , gene expression , biology , in vivo , gene , cancer research , cardioprotection , microbiology and biotechnology , medicine , genetics , ischemia
BetaAR‐mediated transactivation of epidermal growth factor receptor (EGFR) has been shown to promote cardioprotection in a mouse model of heart failure through unknown mechanisms. We hypothesized that this process could impact survival via regulation of gene expression. Thus, acute changes in cardiac gene expression were assessed via RNASeq of C57BL/6 mouse hearts given i.p. injections of isoproterenol in the presence or absence of the EGFR antagonist gefitinib for 1 hour. Total RNA from 4 hearts per treatment group were combined and underwent DNA library generation and SOLiD sequencing analysis, revealing a substantial number of genes regulated by each treatment. Gef alone significantly altered the expression of almost 200 genes compared to control suggesting potential Gef‐dependent alterations in the heart during clinical use. ISO alone and Gef/ISO significantly altered 310 and 481 distinct genes compared to control, respectively. Further statistical analysis was performed, confirming 139 genes significantly altered between the ISO and Gef/ISO groups (ISO‐induced gene up/downregulation antagonized/promoted by Gef), including several genes known to be involved in the regulation of cell death and survival. Thus, BetaAR‐mediated EGFR transactivation induces rapid modulation of cardiac gene expression in response to catecholamine stimulation in vivo.