科研成果详情

题名EGFR inhibition attenuates diabetic nephropathy through decreasing ROS and endoplasmic reticulum stress
作者
发表日期2017-05-16
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diabetic nephropathy epidermal growth factor receptor inhibitor ER stress oxidative stress
其他关键词GROWTH-FACTOR RECEPTOR ; INDUCED APOPTOSIS ; OXIDATIVE STRESS ; KINASE ACTIVATION ; TYROSINE KINASE ; CARDIAC DAMAGE ; ER STRESS ; MECHANISMS ; KIDNEY ; CELLS
摘要Diabetic nephropathy (DN) is a progressive kidney disease due to glomerular capillary damage in diabetic patients. Endoplasmic reticulum (ER) stress caused by reactive oxygen species (ROS) is associated with DN progression. Epidermal growth factor receptor (EGFR) mediates oxidative stress and damage of cardiomyocytes in diabetic mice. Here we demonstrated that AG1478, a specific inhibitor of EGFR, blocked EGFR and AKT phosphorylation in diabetic mice. Oxidative stress and ER stress markers were eliminated after AG1478 administration. AG1478 decreased pro-fibrotic genes TGF-beta and collagen IV. Furthermore, we found that high glucose (HG) induced oxidative stress and ER stress, and subsequently increased ATF4 and CHOP. These changes were eliminated by either AG1478 or ROS scavenger N-acetyl-L-cysteine (NAC) administration. These results were confirmed by knock-down approaches in renal mesangial SV40 cells. However, AG1478, not NAC, reversed HG induced EGFR and AKT phosphorylation. These results suggest that EGFR/AKT/ROS/ER stress signaling plays an essential role in DN development and inhibiting EGFR may serve as a potential therapeutic strategy in diabetic kidney diseases.
资助项目National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81622043, 21572166, 81500657, 81570347]; Natural Science Funding of Zhejiang Province [LR16H310001, LY16H310013, LQ16H160019]; Science and Technology Grant of Wenzhou City [Y20150085]
出版者IMPACT JOURNALS LLC
出版地ORCHARD PARK
ISSN1949-2553
EISSN1949-2553
卷号8期号:20页码:32655-32667
DOI10.18632/oncotarget.15948
页数13
WOS类目Oncology ; Cell Biology
WOS研究方向Oncology ; Cell Biology
WOS记录号WOS:000401767700023
收录类别SCIE ; PUBMED ; SCOPUS
URL查看原文
PubMed ID28427241
PMC记录号PMC5464817
SCOPUSEID2-s2.0-85019231908
通讯作者地址[Liang, Guang]Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou, Zhejiang,325035,China
Scopus学科分类Oncology
引用统计
被引频次:26[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/11950
专题药学院(分析测试中心)
附属第二医院
第二临床医学院、附属第二医院、育英儿童医院
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
其他_附属第五医院(丽水市中心医院)
通讯作者Liang, Guang
作者单位
1.Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou, Zhejiang,325035,China;
2.Department of Ultrasonography,The Second Affiliated Hospital and Yuying Children's Hospital,Wenzhou Medical University,Zhejiang, Wenzhou,325000,China;
3.Department of Interventional Radiology,The Fifth Affiliated Hospital,Wenzhou Medical University,Zhejiang, Lishui,323000,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
Xu, Zheng,Zhao, Yunjie,Zhong, Peng,et al. EGFR inhibition attenuates diabetic nephropathy through decreasing ROS and endoplasmic reticulum stress[J]. ONCOTARGET,2017,8(20):32655-32667.
APA Xu, Zheng., Zhao, Yunjie., Zhong, Peng., Wang, Jingying., Weng, Qiaoyou., ... & Liang, Guang. (2017). EGFR inhibition attenuates diabetic nephropathy through decreasing ROS and endoplasmic reticulum stress. ONCOTARGET, 8(20), 32655-32667.
MLA Xu, Zheng,et al."EGFR inhibition attenuates diabetic nephropathy through decreasing ROS and endoplasmic reticulum stress".ONCOTARGET 8.20(2017):32655-32667.

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