EGFR mediates hyperlipidemia-induced renal injury via regulating inflammation and oxidative stress: the detrimental role and mechanism of EGFR activation

doi:10.18632/oncotarget.8222

科研成果详情

题名	EGFR mediates hyperlipidemia-induced renal injury via regulating inflammation and oxidative stress: the detrimental role and mechanism of EGFR activation
作者	Fang, Qilu 1; Zou, Chunpeng2; Zhong, Peng 1; Lin, Feng 3; Li, Weixin1; Wang, Lintao 1; Zhang, Yali1; Zheng, Chao4; Wang, Yi1; Li, Xiaokun1; Liang, Guang1
发表日期	2016-04-26
发表期刊	ONCOTARGET 影响因子和分区
语种	英语
原始文献类型	Article
关键词	obesity obesity-induced kidney injury epidermal growth factor receptor palmitate c-Src
其他关键词	GROWTH-FACTOR RECEPTOR ; NF-KAPPA-B ; ANGIOTENSIN-II ; INHIBITION PROTECTS ; CURCUMIN ; PATHWAY ; TRANSACTIVATION ; CHEMOTHERAPY ; KIDNEY ; CANCER
摘要	Previous studies have implicated inflammation, oxidative stress, and fibrosis as key factors in the development of obesity-induced kidney diseases. Epidermal growth factor receptor (EGFR) plays an important role in cancer development. Recently, the EGFR pathway has been increasingly implicated in chronic cardiovascular diseases via regulating inflammation and oxidative stress. However, it is unclear if EGFR is involved in obesity-related kidney injury. Using ApoE(-/-) and C57BL/6 mice models and two specific EGFR inhibitors, we investigated the potential effects of EGFR inhibition in the treatment of obesity-related nephropathy and found that EGFR inhibition alleviates renal inflammation, oxidative stress and fibrosis. In NRK-52E cells, we also elucidated the mechanism behind hyperlipidemia-induced EGFR activation. We observed that c-Src and EGFR forms a complex, and following PA stimulation, it is the successive phosphorylation, not formation, of the c-Src/EGFR complex that results in the subsequent cascade activation. Second, we found that TLR4 regulates the activation EGFR pathway mainly through the phosphorylation of the c-Src/EGFR complex. These results demonstrate the detrimental role of EGFR in the pathogenesis of obesity-related nephropathy, provide a new understanding of the mechanism behind hyperlipidemia/FFA-induced EGFR activation, and support the use of EGFR inhibitors in the treatment of obesity-induced kidney diseases.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81500657, 81503123]; High-level Innovative Talent Funding of Zhejiang Department of Health [2010-017]; Zhejiang Provincial Education Research Project [Y201430483]; Wenzhou city Science and Technology Project [20140309]
出版者	IMPACT JOURNALS LLC
出版地	ORCHARD PARK
ISSN	1949-2553
EISSN	1949-2553
卷号	7 期号:17 页码:24361-24373
DOI	10.18632/oncotarget.8222
页数	13
WOS类目	Oncology ; Cell Biology
WOS研究方向	Oncology ; Cell Biology
WOS记录号	WOS:000377706200105
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	27014908
PMC记录号	PMC5029707
SCOPUSEID	2-s2.0-84966559954
通讯作者地址	[Liang, Guang]Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou, Zhejiang,China
Scopus学科分类	Oncology
引用统计	被引频次：29[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/14730
专题	药学院（分析测试中心）附属第二医院附属第一医院第二临床医学院、附属第二医院、育英儿童医院第一临床医学院（信息与工程学院）、附属第一医院_妇产科学_妇科第二临床医学院、附属第二医院、育英儿童医院_影像医学与核医学_超声科
通讯作者	Liang, Guang
作者单位	1.Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou, Zhejiang,China; 2.Department of Ultrasonography,The Second Affiliated Hospital,Wenzhou Medical University,Wenzhou, Zhejiang,China; 3.Department of Gynecology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou, Zhejiang,China; 4.Department of Endocrinology,The Second Affiliated Hospital,Wenzhou Medical University,Wenzhou, Zhejiang,China
第一作者单位	药学院（分析测试中心）; 生物有机与药物化学研究中心
通讯作者单位	药学院（分析测试中心）; 生物有机与药物化学研究中心
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Fang, Qilu,Zou, Chunpeng,Zhong, Peng,et al. EGFR mediates hyperlipidemia-induced renal injury via regulating inflammation and oxidative stress: the detrimental role and mechanism of EGFR activation[J]. ONCOTARGET,2016,7(17):24361-24373.
APA	Fang, Qilu., Zou, Chunpeng., Zhong, Peng., Lin, Feng., Li, Weixin., ... & Liang, Guang. (2016). EGFR mediates hyperlipidemia-induced renal injury via regulating inflammation and oxidative stress: the detrimental role and mechanism of EGFR activation. ONCOTARGET, 7(17), 24361-24373.
MLA	Fang, Qilu,et al."EGFR mediates hyperlipidemia-induced renal injury via regulating inflammation and oxidative stress: the detrimental role and mechanism of EGFR activation".ONCOTARGET 7.17(2016):24361-24373.