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外科科室普通外科广东省人民医院[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临床科室重症医学科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：
National Natural Science Foundation of China [81301664, 81173168]; 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：
通讯机构：[1]The Department of Anesthesia, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
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):35478-95.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):35478-95
