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Basic fibroblast growth factor protects against influenza A virus-induced acute lung injury by recruiting neutrophils Free
Keyu Wang 1,† , Chengcai Lai 1,† , Tieling Li 2 , Cheng Wang 2 , Wei Wang 3 , Bing Ni 4 , Changqing Bai 5 , Shaogeng Zhang 6 , Lina Han 2 , Hongjing Gu 1 , Zhongpeng Zhao 1 , Yueqiang Duan 1 , Xiaolan Yang 1 , Li Xing 1 , Lingna Zhao 1 , Shanshan Zhou 1 , Min Xia 1 , Chengyu Jiang 3,* , Xiliang Wang 1,* , and Penghui Yang 1,6,*
1 State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China
2 Chinese PLA General Hospital, Beijing 100853, China
3 State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China
4 Institute of Immunology, Third Military Medical University, Chongqing 400038, China
5 Beijing 307 Hospital of PLA Affiliated with the Chinese Academy of Medical Sciences, Beijing 100070, China
6 Beijing 302 Hospital of PLA, Beijing 100039, China
These authors contributed equally to this work.
*Correspondence to:* Correspondence to: Penghui Yang, E-mail: ypenghuiamms@hotmail.com; Xiliang Wang, E-mail: xiliangw@126.com; Chengyu Jiang, E-mail: jiang@pumc.edu.cn
J Mol Cell Biol, Volume 10, Issue 6, December 2018, Pages 573-585  https://doi.org/10.1093/jmcb/mjx047
Keyword: influenza H1N1 virus, recombinant FGF2 protein, neutrophil recruitment, FGFR2–PI3K–AKT–NFκB signaling, therapeutic target

Influenza virus (IAV) infection is a major cause of severe respiratory illness that affects almost every country in the world. IAV infections result in respiratory illness and even acute lung injury and death, but the underlying mechanisms responsible for IAV pathogenesis have not yet been fully elucidated. In this study, the basic fibroblast growth factor 2 (FGF2) level was markedly increased in H1N1 virus-infected humans and mice. FGF2, which is predominately derived from epithelial cells, recruits and activates neutrophils via the FGFR2–PI3K–AKT–NFκB signaling pathway. FGF2 depletion or knockout exacerbated influenza-associated disease by impairing neutrophil recruitment and activation. More importantly, administration of the recombinant FGF2 protein significantly alleviated the severity of IAV-induced lung injury and promoted the survival of IAV-infected mice. Based on the results from experiments in which neutrophils were depleted and adoptively transferred, FGF2 protected mice against IAV infection by recruiting neutrophils. Thus, FGF2 plays a critical role in preventing IAV-induced lung injury, and FGF2 is a promising potential therapeutic target during IAV infection.