Fibroblast growth factor 18 alleviates stress-induced pathological cardiac hypertrophy in male mice

doi:10.1038/s41467-023-36895-1

科研成果详情

题名	Fibroblast growth factor 18 alleviates stress-induced pathological cardiac hypertrophy in male mice
作者	Chen, Gen1,2,3,4; An, Ning 5; Shen, Jingling 6; Chen, Huinan 1; Chen, Yunjie 7; Sun, Jia 1; Hu, Zhicheng 2; Qiu, Junhui1; Jin, Cheng 1; He, Shengqu1; Mei, Lin 8; Sui, Yanru 1; Li, Wanqian 9; Chen, Peng 10; Guan, Xueqiang10; Chu, Maoping11; Wang, Yang 12; Jin, Litai1; Kim, Kwonseop 3; Li, Xiaokun1,2; Cong, Weitao1,2; Wang, Xu 1
发表日期	2023-03-04
发表期刊	Nature communications 影响因子和分区
语种	英语
原始文献类型	Journal Article
其他关键词	OXIDATIVE STRESS ; NADPH OXIDASES ; MITOCHONDRIAL DYSFUNCTION ; NOX4 ; PROLIFERATION ; PREVENTION ; SPRIFERMIN ; RECEPTORS ; MIGRATION ; APOPTOSIS
摘要	Fibroblast growth factor-18 (FGF18) has diverse organ development and damage repair roles. However, its role in cardiac homeostasis following hypertrophic stimulation remains unknown. Here we investigate the regulation and function of the FGF18 in pressure overload (PO)-induced pathological cardiac hypertrophy. FGF18 heterozygous (Fgf18+/-) and inducible cardiomyocyte-specific FGF18 knockout (Fgf18-CKO) male mice exposed to transverse aortic constriction (TAC) demonstrate exacerbated pathological cardiac hypertrophy with increased oxidative stress, cardiomyocyte death, fibrosis, and dysfunction. In contrast, cardiac-specific overexpression of FGF18 alleviates hypertrophy, decreased oxidative stress, attenuates cardiomyocyte apoptosis, and ameliorates fibrosis and cardiac function. Tyrosine-protein kinase FYN (FYN), the downstream factor of FGF18, was identified by bioinformatics analysis, LC-MS/MS and experiment validation. Mechanistic studies indicate that FGF18/FGFR3 promote FYN activity and expression and negatively regulate NADPH oxidase 4 (NOX4), thereby inhibiting reactive oxygen species (ROS) generation and alleviating pathological cardiac hypertrophy. This study uncovered the previously unknown cardioprotective effect of FGF18 mediated by the maintenance of redox homeostasis through the FYN/NOX4 signaling axis in male mice, suggesting a promising therapeutic target for the treatment of cardiac hypertrophy
资助项目	National Natural Science Foundation of China [82170365, 82070507, 81870209, 81770498, 81773346]; Zhejiang Provincial Natural Science Foundation [LY19H020005, LY21H020009, LQ23H020003]; Zhejiang Province Medical and Health Science Program [2019KY099]; Wenzhou Municipal Science and Technology Bureau Foundation [Y2020180]; Ningbo Natural Science Foundation [2022J265]
出版者	NATURE PORTFOLIO
ISSN	2041-1723
EISSN	2041-1723
卷号	14 期号:1
DOI	10.1038/s41467-023-36895-1
页数	18
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
WOS记录号	WOS:000943946800009
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	36871047
SCOPUSEID	2-s2.0-85149540354
自科自定义期刊分类	T2(B)类
通讯作者地址	[Li, Xiaokun]School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,325035,China ; [Cong, Weitao]School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,325035,China ; [Wang, Xu]School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,325035,China
Scopus学科分类	Chemistry (all);Biochemistry, Genetics and Molecular Biology (all);Physics and Astronomy (all)
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/172908
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、育英儿童医院基础医学院（机能实验教学中心）_形态学系_组织胚胎学其他_瓯江实验室
通讯作者	Li, Xiaokun; Cong, Weitao; Wang, Xu
作者单位	1.School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,325035,China; 2.Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine,Vision and Brain Health),School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,China; 3.College of Pharmacy,Chonnam National University,Gwangju,61186,South Korea; 4.Department of Physiology and Pharmacology,School of Basic Medical Sciences,Health Science Center,Ningbo University,Ningbo,315211,China; 5.Department of Pharmacy,The Affiliated Li Huili Hospital,Ningbo University,Ningbo,315040,China; 6.Institute of Life Sciences,College of Life and Environmental Sciences,Wenzhou University,Wenzhou,325035,China; 7.Department of Pharmacy,Ningbo First Hospital,Ningbo,315010,China; 8.Department of Pharmacy,Xiamen Medical College,Xiamen,361023,China; 9.Pharmacy Department,Taizhou Municipal Hospital,Taizhou,318000,China; 10.Department of Cardiology,The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Wenzhou,325027,China; 11.Pediatric Research Institute,The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Wenzhou,325027,China; 12.Department of Histology and Embryology,Institute of Neuroscience,Wenzhou Medical University,Wenzhou,325035,China
第一作者单位	温州医科大学; 瓯江实验室
通讯作者单位	温州医科大学
第一作者的第一单位	温州医科大学
推荐引用方式 GB/T 7714	Chen, Gen,An, Ning,Shen, Jingling,et al. Fibroblast growth factor 18 alleviates stress-induced pathological cardiac hypertrophy in male mice[J]. Nature communications,2023,14(1).
APA	Chen, Gen., An, Ning., Shen, Jingling., Chen, Huinan., Chen, Yunjie., ... & Wang, Xu. (2023). Fibroblast growth factor 18 alleviates stress-induced pathological cardiac hypertrophy in male mice. Nature communications, 14(1).
MLA	Chen, Gen,et al."Fibroblast growth factor 18 alleviates stress-induced pathological cardiac hypertrophy in male mice".Nature communications 14.1(2023).