题名 | Inhibition of STAT3 activation mediated by toll-like receptor 4 attenuates angiotensin II-induced renal fibrosis and dysfunction |
作者 | |
发表日期 | 2019-07 |
发表期刊 | BRITISH JOURNAL OF PHARMACOLOGY 影响因子和分区 |
语种 | 英语 |
原始文献类型 | Article |
其他关键词 | PHARMACOLOGY 2017/18 ; CONCISE GUIDE ; SIGNALING PATHWAY ; OXIDATIVE STRESS ; EPITHELIAL-CELLS ; EXPRESSION ; RESPONSES ; PROTECTS ; BURDEN ; TLR4 |
摘要 | Background and Purpose Hypertension adversely affects the kidney and is the second leading cause of kidney failure. Overproduction of angiotensin II greatly contributes to the progression of hypertensive kidney disease. Angiotensin II has recently been shown to activate STAT3 in cardiovascular cells. However, the underlying mechanisms of STAT3 activation by angiotensin II and downstream functional consequences in the kidneys are not fully understood. Experimental Approach C57BL/6 mice were treated with angiotensin II by subcutaneous infusion for 1 month to develop nephropathy. Mice were treated with either adeno-associated virus expressing STAT3 shRNA or STAT3 inhibitor, S3I-201. Human archival kidney samples from five patients with hypertension and five individuals without hypertension were also examined. In vitro, STAT3 was blocked using siRNA or STAT3 inhibitor S3I-201 in the renal proximal tubular cell line, NRK52E, after exposure to angiotensin II. Key Results Angiotensin II activated STAT3 in kidney epithelial cells through engaging toll-like receptor 4 (TLR4) and JAK2, which was independent of IL-6/gp130 and angiotensin AT(1) receptors. Angiotensin II-mediated STAT3 activation increased fibrotic proteins and resulted in renal dysfunction. Both STAT3 inhibition by the low MW compound S3I-201 and TLR4 deficiency normalized renal fibrosis and dysfunction caused by Ang II in mice, without affecting hypertension. Conclusions and Implications Our study reveals a novel mechanism of STAT3 activation, induced by angiotensin II, in kidney tissues and highlights a translational significance of a STAT3 inhibitor as potential therapeutic agent for hypertensive kidney disease. |
资助项目 | Natural Science Foundation of Zhejiang ProvinceNatural Science Foundation of Zhejiang Province [LR16H310001, LY18H310012]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81570347, 81600659, 81622043]; National Key Research Project [2017YFA0506000] |
出版者 | WILEY |
出版地 | HOBOKEN |
ISSN | 0007-1188 |
EISSN | 1476-5381 |
卷号 | 176期号:14页码:2627-2641 |
DOI | 10.1111/bph.14686 |
页数 | 15 |
WOS类目 | Pharmacology & Pharmacy |
WOS研究方向 | Pharmacology & Pharmacy |
WOS记录号 | WOS:000472784200020 |
收录类别 | SCIE ; PUBMED ; SCOPUS |
URL | 查看原文 |
PubMed ID | 30958891 |
PMC记录号 | PMC6592868 |
SCOPUSEID | 2-s2.0-85065718693 |
自科自定义期刊分类 | T3(B)类 |
通讯作者地址 | [Liang, Guang]Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,China |
Scopus学科分类 | Pharmacology |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.wmu.edu.cn/handle/3ETUA0LF/1396 |
专题 | 药学院(分析测试中心) 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,China; 2.Department of Ultrasonography,The Second Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 3.Department of Endocrinology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,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,Zou, Chunpeng,Yu, Weihui,et al. Inhibition of STAT3 activation mediated by toll-like receptor 4 attenuates angiotensin II-induced renal fibrosis and dysfunction[J]. BRITISH JOURNAL OF PHARMACOLOGY,2019,176(14):2627-2641. |
APA | Xu, Zheng., Zou, Chunpeng., Yu, Weihui., Xu, Sujing., Huang, Lan., ... & Wang, Yi. (2019). Inhibition of STAT3 activation mediated by toll-like receptor 4 attenuates angiotensin II-induced renal fibrosis and dysfunction. BRITISH JOURNAL OF PHARMACOLOGY, 176(14), 2627-2641. |
MLA | Xu, Zheng,et al."Inhibition of STAT3 activation mediated by toll-like receptor 4 attenuates angiotensin II-induced renal fibrosis and dysfunction".BRITISH JOURNAL OF PHARMACOLOGY 176.14(2019):2627-2641. |
条目包含的文件 | 条目无相关文件。 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论