Ang II (Angiotensin II)-Induced FGFR1 (Fibroblast Growth Factor Receptor 1) Activation in Tubular Epithelial Cells Promotes Hypertensive Kidney Fibrosis and Injury

doi:10.1161/HYPERTENSIONAHA.122.18657

科研成果详情

题名	Ang II (Angiotensin II)-Induced FGFR1 (Fibroblast Growth Factor Receptor 1) Activation in Tubular Epithelial Cells Promotes Hypertensive Kidney Fibrosis and Injury
作者	Xu, Zheng 1; Luo, Wu1; Chen, Lingfeng 2,3; Zhuang, Zaishou 4; Yang, Daona4; Qian, Jianchang1; Khan, Zia A.5,6; Guan, Xinfu 4; Wang, Yi1; Li, Xiaokun1; Liang, Guang1,2
发表日期	2022-09
发表期刊	HYPERTENSION 影响因子和分区
语种	英语
原始文献类型	Article
关键词	angiotensin II animals humans hypertension renal insufficiency chronic
其他关键词	TRANSCRIPTION-3 BINDING ; KINASE ; EXPRESSION ; TRANSDUCTION ; INHIBITOR ; AZD4547 ; CANCER
摘要	Background: Elevated Ang II (angiotensin II) level leads to a range of conditions, including hypertensive kidney disease. Recent evidences indicate that FGFR1 (fibroblast growth factor receptor 1) signaling may be involved in kidney injuries. In this study, we determined whether Ang II alters FGFR1 signaling to mediate renal dysfunction. Methods: Human archival kidney samples from patients with or without hypertension were examined. Multiple genetic and pharmacological approaches were used to investigate FGFR1-mediated signaling in tubular epithelial NRK-52E cells in response to Ang II stimulation. C57BL/6 mice were infused with Ang II for 28 days to develop hypertensive kidney disease. Mice were treated with either adeno-associated virus expressing FGFR1 shRNA or FGFR1 inhibitor AZD4547. Results: Kidney specimens from subjects with hypertension and mice challenged with Ang II have increased FGFR1 activity in renal epithelial cells. Renal epithelial cells in culture initiate extracellular matrix programming in response to Ang II, through the activation of FGFR1, which is independent of both AT1R (angiotensin II receptor type 1) and AT2R (angiotensin II receptor type 2). The RNA sequencing analysis indicated that disrupting FGFR1 suppresses Ang II-induced fibrogenic responses in epithelial cells. Mechanistically, Ang II-activated FGFR1 leads to STAT3 (signal transducer and activator of transcription 3) activation, which is responsible for fibrogenic factor expression in kidneys. In the mouse model of hypertensive kidney disease, genetic knockdown of FGFR1 or pharmacological inhibition of its activity protected kidneys from dysfunction and fibrosis upon Ang II challenge. Conclusions: Our studies uncover a novel mechanism causing renal fibrosis in hypertension and indicate FGFR1 as a potential target to preserve renal function and integrity.
资助项目	National Key Research Project [2017YFA0506000]; National Natural Science Foundation of China [82000793, 81930108, 81803600, 81770799]; Zhejiang Provincial Natural Science Foundation of China [LQ22H020002]; Wenzhou Science and Technology Key Project [2018ZY009]; Wenzhou Science and Technology Basic Medical Project [Y20210187]
出版者	LIPPINCOTT WILLIAMS & WILKINS
出版地	PHILADELPHIA
ISSN	0194-911X
EISSN	1524-4563
卷号	79 期号:9 页码:2028-2041
DOI	10.1161/HYPERTENSIONAHA.122.18657
页数	14
WOS类目	Peripheral Vascular Disease
WOS研究方向	Cardiovascular System & Cardiology
WOS记录号	WOS:000838820400017
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	35862110
SCOPUSEID	2-s2.0-85135974927
通讯作者地址	[Liang, Guang]School of Pharmaceutical Sciences,Hangzhou Medical College,Hanzhou,311399,China
Scopus学科分类	Internal Medicine
TOP期刊	TOP期刊
引用统计	被引频次：1[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/154174
专题	药学院（分析测试中心）_生物有机与药物化学研究中心附属第一医院其他_附属苍南医院（苍南县人民医院）
通讯作者	Liang, Guang
作者单位	1.Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Zhejiang,China; 2.School of Pharmaceutical Sciences,Hangzhou Medical College,Hanzhou,311399,China; 3.Department of Cardiology and Medical Research Center,The First Affiliated Hospital,Wenzhou Medical University,Zhejiang,China; 4.The Affiliated Cangnan Hospital,Wenzhou Medical University,Zhejiang,China; 5.Department of Pathology and Laboratory Medicine,University of Western Ontario,London,Canada; 6.Wenzhou Institute,University of Chinese Academy of Sciences,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
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,Luo, Wu,Chen, Lingfeng,et al. Ang II (Angiotensin II)-Induced FGFR1 (Fibroblast Growth Factor Receptor 1) Activation in Tubular Epithelial Cells Promotes Hypertensive Kidney Fibrosis and Injury[J]. HYPERTENSION,2022,79(9):2028-2041.
APA	Xu, Zheng., Luo, Wu., Chen, Lingfeng., Zhuang, Zaishou., Yang, Daona., ... & Liang, Guang. (2022). Ang II (Angiotensin II)-Induced FGFR1 (Fibroblast Growth Factor Receptor 1) Activation in Tubular Epithelial Cells Promotes Hypertensive Kidney Fibrosis and Injury. HYPERTENSION, 79(9), 2028-2041.
MLA	Xu, Zheng,et al."Ang II (Angiotensin II)-Induced FGFR1 (Fibroblast Growth Factor Receptor 1) Activation in Tubular Epithelial Cells Promotes Hypertensive Kidney Fibrosis and Injury".HYPERTENSION 79.9(2022):2028-2041.