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 |
ISSN | 1949-2553 |
EISSN | 1949-2553 |
卷号 | 8期号:20页码:32655-32667 |
DOI | 10.18632/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 ID | 28427241 |
PMC记录号 | PMC5464817 |
SCOPUSEID | 2-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 | |
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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