FAK mediates LPS-induced inflammatory lung injury through interacting TAK1 and activating TAK1-NF kappa B pathway

doi:10.1038/s41419-022-05046-7

科研成果详情

题名	FAK mediates LPS-induced inflammatory lung injury through interacting TAK1 and activating TAK1-NF kappa B pathway
作者	Chen, Xi 1,2; Zhao, Ying1; Wang, Xu 1; Lin, Yimin1; Zhao, Weixin1; Wu, Di1; Pan, Jingye3; Luo, Wu 3; Wang, Yi 1; Liang, Guang1,4,5
发表日期	2022-07-08
发表期刊	CELL DEATH & DISEASE 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	FOCAL ADHESION KINASE ; RESPIRATORY-DISTRESS-SYNDROME ; NECROSIS-FACTOR-ALPHA ; NF-KAPPA-B ; INTERLEUKIN-8 ; FIBROBLAST ; DIFFERENTIATION ; IDENTIFICATION ; EPIDEMIOLOGY ; PATHOGENESIS
摘要	Acute lung injury (ALI), characterized by inflammatory damage, is a major clinical challenge. Developing specific treatment options for ALI requires the identification of novel targetable signaling pathways. Recent studies reported that endotoxin lipopolysaccharide (LPS) induced a TLR4-dependent activation of focal adhesion kinase (FAK) in colorectal adenocarcinoma cells, suggesting that FAK may be involved in LPS-induced inflammatory responses. Here, we investigated the involvement and mechanism of FAK in mediating LPS-induced inflammation and ALI. We show that LPS phosphorylates FAK in macrophages. Either FAK inhibitor, site-directly mutation, or siRNA knockdown of FAK significantly suppresses LPS-induced inflammatory cytokine production in macrophages. FAK inhibition also blocked LPS-induced activation of MAPKs and NF kappa B. Mechanistically, we demonstrate that activated FAK directly interacts with transforming growth factor-beta-activated kinase-1 (TAK1), an upstream kinase of MAPKs and NF kappa B, and then phosphorylates TAK1 at Ser412. In a mouse model of LPS-induced ALI, pharmacological inhibition of FAK suppressed FAK/TAK activation and inflammatory response in lung tissues. These activities resulted in the preservation of lung tissues in LPS-challenged mice and increased survival during LPS-induced septic shock. Collectively, our results illustrate a novel FAK-TAK1-NF kappa B signaling axis in LPS-induced inflammation and ALI, and support FAK as a potential target for the treatment of ALI.
资助项目	National Key Research Project [2017YFA0506000]; National Natural Science Foundation of China [81971143, 82003644, 81803345, 82000793]; Zhejiang Provincial Key Scientific Project [2021C03041]
出版者	SPRINGERNATURE
出版地	LONDON
ISSN	2041-4889
卷号	13 期号:7 页码:589
DOI	10.1038/s41419-022-05046-7
页数	12
WOS类目	Cell Biology
WOS研究方向	Cell Biology
WOS记录号	WOS:000822357200001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	35803916
SCOPUSEID	2-s2.0-85133650797
通讯作者地址	[Liang, Guang]Chemical Biology Research Center,School of Pharmaceutical Science,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China
Scopus学科分类	Immunology;Cellular and Molecular Neuroscience;Cell Biology;Cancer Research
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/154427
专题	药学院（分析测试中心）附属第一医院附属第一医院_重症医学科（ICU）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	Liang, Guang
作者单位	1.Chemical Biology Research Center,School of Pharmaceutical Science,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 2.Department of Pharmacology,Medical College,Taizhou University,Taizhou,Zhejiang,Jiaojiang,318000,China; 3.Department of Critical Care Medicine and Medical Research Center,the First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China; 4.School of Pharmaceutical Sciences,Hangzhou Medical College,Zhejiang,Hangzhou,311399,China; 5.Wenzhou Institute,University of Chinese Academy of Sciences,Zhejiang,Wenzhou,325001,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	Chen, Xi,Zhao, Ying,Wang, Xu,et al. FAK mediates LPS-induced inflammatory lung injury through interacting TAK1 and activating TAK1-NF kappa B pathway[J]. CELL DEATH & DISEASE,2022,13(7):589.
APA	Chen, Xi., Zhao, Ying., Wang, Xu., Lin, Yimin., Zhao, Weixin., ... & Liang, Guang. (2022). FAK mediates LPS-induced inflammatory lung injury through interacting TAK1 and activating TAK1-NF kappa B pathway. CELL DEATH & DISEASE, 13(7), 589.
MLA	Chen, Xi,et al."FAK mediates LPS-induced inflammatory lung injury through interacting TAK1 and activating TAK1-NF kappa B pathway".CELL DEATH & DISEASE 13.7(2022):589.