机构：[1]The Department of Anesthesia, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.[2]The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China.[3]The Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, Guangdong, China.广东省人民医院[4]The Department of Laboratory Medicine, First Affiliated Hospital of Ganna Medical University, Ganzhou, Jiangxi, China.[5]The Department of Intensive Care Unit, BaYi Children's Hospital, Beijing Military General Hospital, Beijing, China.首都医科大学附属北京儿童医院
To study the effect of EGFR activation on the generation of TNF-α and the occurrence of cardiac dysfuncetion during sepsis, PD168393 and erlotinib (both are EGFR inhibitors) were applied to decreased the production of TNF-α and phosphrylation of ERK1/2 and p38 induced by LPS in cardiomyocytes. These results were further proved by specifically knocked down the expression of EGFR in vitro. Both TAPI-1, a TNF-α converting enzyme (TACE) inhibitor, and TGF-α neutralizing antibody could inhibit the activation of EGFR and the generation of TNF-α mRNA after LPS treatment. The increase of TGF-α in response to LPS could also be suppressed by TAPI-1. On the other hand, exogenous TGF-α increased the expression of TNF-α mRNA and partially reversed the inhibitory effect of TAPI-1 on expression of TNF-α mRNA in response to LPS indicating that the transactivation of EGFR by LPS in cardiomyocytes needs the help of TACE and TGF-α. In endotoxemic mice, inhibition the activation of EGFR not only decreased TNF-α production in the myocardium but also improved left ventricular pump function and ameliorated cardiac dysfunction and ultimately improved survival rate. All these results provided a new insight of how EGFR regulation the production of TNF-α in cardiomyocytes and a potential new target for the treatment of cardiac dysfunction in sepsis.
基金：
the National Natural Science Foundation of China (81301664 and 81173168) and the Natural Science Foundation of Guangdong Province (S2013010014312)
第一作者机构：[1]The Department of Anesthesia, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.[2]The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Sun Xuegang,Liang Jiani,Yao Xueqing,et al.The activation of EGFR promotes myocardial tumor necrosis factor-α production and cardiac failure in endotoxemia.[J].ONCOTARGET.2015,6(34):35478-35495.doi:10.18632/oncotarget.6071.
APA：
Sun Xuegang,Liang Jiani,Yao Xueqing,Lu Chunhua,Zhong Tianyu...&Tang Jing.(2015).The activation of EGFR promotes myocardial tumor necrosis factor-α production and cardiac failure in endotoxemia..ONCOTARGET,6,(34)
MLA：
Sun Xuegang,et al."The activation of EGFR promotes myocardial tumor necrosis factor-α production and cardiac failure in endotoxemia.".ONCOTARGET 6..34(2015):35478-35495
