Novel Epidermal Growth Factor Receptor Inhibitor Attenuates Angiotensin II-Induced Kidney Fibrosiss

doi:10.1124/jpet.115.228080

科研成果详情

题名	Novel Epidermal Growth Factor Receptor Inhibitor Attenuates Angiotensin II-Induced Kidney Fibrosiss
作者	Qian, Yuanyuan1; Peng, Kesong1; Qiu, Chenyu 1; Skibba, Melissa 1; Huang, Yi 1; Xu, Zheng1; Zhang, Yali 1; Hu, Jie 1; Liang, Dandan1; Zou, Chunpeng2; Wang, Yi 1; Liang, Guang1
发表日期	2016-01
发表期刊	JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	UNILATERAL URETERAL OBSTRUCTION ; ENDOPLASMIC-RETICULUM STRESS ; RENAL FIBROSIS ; DIABETIC-NEPHROPATHY ; TYROSINE KINASES ; ACTIVATION ; DISEASE ; TRANSACTIVATION ; PROGRESSION ; EXPRESSION
摘要	Chronic activation of renin-angiotensin system (RAS) greatly contributes to renal fibrosis and accelerates the progression of chronic kidney disease; however, the underlying molecular mechanism is poorly understood. Angiotensin II (Ang II), the central component of RAS, is a key regulator of renal fibrogenic destruction. Here we show that epidermal growth factor receptor (EGFR) plays an important role in Ang II-induced renal fibrosis. Inhibition of EGFR activation by novel small molecules or by short hairpin RNA knockdown in Ang II-treated SV40 mesangial cells in vitro suppresses protein kinase B and extracellular signal-related kinase signaling pathways and transforming growth factor-beta/Sma-and Mad-related protein activation, and abolishes the accumulation of fibrotic markers such as connective tissue growth factor, collagen IV. The transactivation of EGFR by Ang II in SV40 cells depends on the phosphorylation of proto-oncogene tyrosine-protein kinase Src (c-Src) kinase. Further validation in vivo demonstrates that EGFR small molecule inhibitor successfully attenuates renal fibrosis and kidney dysfunction in a mouse model induced by Ang II infusion. These findings indicate a crucial role of EGFR in Ang II-dependent renal deterioration, and reveal EGFR inhibition as a new therapeutic strategy for preventing progression of chronic renal diseases.
资助项目	National Natural Science Funding of ChinaNational Natural Science Foundation of China (NSFC) [81503123, 81502912, 21472142]; Zhejiang Provincial Natural Science Funding [LQ15H120005, LQ14H310003, LY13H060007]; High-Level Innovative Talent Funding of Zhejiang Department of Health [2010-017]
出版者	AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
出版地	BETHESDA
ISSN	0022-3565
EISSN	1521-0103
卷号	356 期号:1 页码:32-42
DOI	10.1124/jpet.115.228080
页数	11
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000366942000005
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	26514795
SCOPUSEID	2-s2.0-84965089223
通讯作者地址	[Liang, Guang]Chemical Biology Research Center,School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou, Zhejiang,325035,China
Scopus学科分类	Molecular Medicine;Pharmacology
引用统计	被引频次：22[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/1287
专题	药学院（分析测试中心）第二临床医学院、附属第二医院、育英儿童医院药学院（分析测试中心）_生物有机与药物化学研究中心第二临床医学院、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 Science,Wenzhou Medical University,Wenzhou, Zhejiang,325035,China; 2.Department of Ultrasonography,2nd Affiliated Hospital,Wenzhou Medical University,Wenzhou, Zhejiang,China
第一作者单位	生物有机与药物化学研究中心
通讯作者单位	生物有机与药物化学研究中心
第一作者的第一单位	生物有机与药物化学研究中心
推荐引用方式 GB/T 7714	Qian, Yuanyuan,Peng, Kesong,Qiu, Chenyu,et al. Novel Epidermal Growth Factor Receptor Inhibitor Attenuates Angiotensin II-Induced Kidney Fibrosiss[J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS,2016,356(1):32-42.
APA	Qian, Yuanyuan., Peng, Kesong., Qiu, Chenyu., Skibba, Melissa., Huang, Yi., ... & Liang, Guang. (2016). Novel Epidermal Growth Factor Receptor Inhibitor Attenuates Angiotensin II-Induced Kidney Fibrosiss. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 356(1), 32-42.
MLA	Qian, Yuanyuan,et al."Novel Epidermal Growth Factor Receptor Inhibitor Attenuates Angiotensin II-Induced Kidney Fibrosiss".JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 356.1(2016):32-42.