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

Gen Chen, Ning An, Jingling Shen, Huinan Chen, Yunjie Chen, Jia Sun, Zhicheng Hu, Junhui Qiu, Cheng Jin, Shengqu He, Lin Mei, Yanru Sui, Wanqian Li, Peng Chen, Xueqiang Guan, Maoping Chu, Yang Wang, Litai Jin, Kwonseop Kim, Xiaokun Li (), Weitao Cong () and Xu Wang ()
Additional contact information
Gen Chen: Wenzhou Medical University
Ning An: The Affiliated Li Huili Hospital, Ningbo University
Jingling Shen: Wenzhou University
Huinan Chen: Wenzhou Medical University
Yunjie Chen: Ningbo First Hospital
Jia Sun: Wenzhou Medical University
Zhicheng Hu: Wenzhou Medical University
Junhui Qiu: Wenzhou Medical University
Cheng Jin: Wenzhou Medical University
Shengqu He: Wenzhou Medical University
Lin Mei: Xiamen Medical College
Yanru Sui: Wenzhou Medical University
Wanqian Li: Taizhou Municipal Hospital
Peng Chen: The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University
Xueqiang Guan: The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University
Maoping Chu: The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University
Yang Wang: Wenzhou Medical University
Litai Jin: Wenzhou Medical University
Kwonseop Kim: Chonnam National University
Xiaokun Li: Wenzhou Medical University
Weitao Cong: Wenzhou Medical University
Xu Wang: Wenzhou Medical University

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-36895-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36895-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-36895-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().