FGF10 attenuates allergic airway inflammation in asthma by inhibiting PI3K/AKT/NF-κB pathway

Wenjun Peng; Yansha Song; Guiping Zhu; Yingying Zeng; Hui Cai; Chong Lu; Zilinuer Abuduxukuer; Xixi Song; Xin Gao; Ling Ye; Jian Wang; Meiling Jin

doi:10.1016/j.cellsig.2023.110964

FGF10 attenuates allergic airway inflammation in asthma by inhibiting PI3K/AKT/NF-κB pathway

Cell Signal. 2024 Jan:113:110964. doi: 10.1016/j.cellsig.2023.110964. Epub 2023 Nov 11.

Authors

Wenjun Peng¹, Yansha Song¹, Guiping Zhu¹, Yingying Zeng¹, Hui Cai², Chong Lu¹, Zilinuer Abuduxukuer¹, Xixi Song¹, Xin Gao¹, Ling Ye¹, Jian Wang², Meiling Jin³

Affiliations

¹ Department of Allergy, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of Pulmonary and Critical Care Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
² Department of Pulmonary and Critical Care Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
³ Department of Allergy, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of Pulmonary and Critical Care Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: mljin118@163.com.

PMID: 37956773
DOI: 10.1016/j.cellsig.2023.110964

Abstract

Background: The effect of fibroblast growth factor 10 (Fgf10) against allergic asthma has remained unclear, despite its importance in lung development and homeostasis maintenance. The purpose of this study was to investigate the protective effect and potential mechanism of Fgf10 on asthma.

Method: House Dust Mite (HDM)-induced asthma mice were administered recombinant Fgf10 intranasally during activation. Flow cytometry and ELISA were performed to determine type of inflammatory cells and type 2 cytokines levels in bronchoalveolar lavage fluid (BALF). Hematoxylin and eosin (H&E) and periodic acid - Schiff (PAS) staining of lung sections were conducted to evaluate histopathological assessment. Transcriptome profiling was analyzed using RNA-seq, followed by bioinformatics and network analyses to investigate the potential mechanisms of Fgf10 in asthma. RT-qPCR was also used to search for and validate differentially expressed genes in human Peripheral Blood Mononuclear Cells (PBMCs).

Results: Exogenous administration of Fgf10 alleviated HDM-induced inflammation and mucus secretion in lung tissues of mice. Fgf10 also significantly inhibited the accumulation of eosinophils and type 2 cytokines (IL-4, IL-5, and IL-13) in BALF. The PI3K/AKT/NF-κB pathway may mediate the suppressive impact of Fgf10 on the asthma inflammation. Through RNA-seq analysis, the intersection of 71 differentially expressed genes (DEGs) was found between HDM challenge and Fgf10 treatment. GO and KEGG enrichment analyses indicated a strong correlation between the DEGs and different immune response. Immune infiltration analysis predicted the differential infiltration of five types of immune cells, such as NK cells, dendritic cells, monocytes and M1 macrophages. PPI analysis determined hub genes such as Irf7, Rsad2, Isg15 and Rtp4. Interestingly, above genes were consistently altered in human PBMCs in asthmatic patients.

Conclusion: Asthma airway inflammation could be attenuated by Fgf10 in this study, suggesting that it could be a potential therapeutic target.

Keywords: Asthma; Fgf10; Inflammation; RNA sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Asthma* / drug therapy
Asthma* / metabolism
Cytokines / metabolism
Disease Models, Animal
Fibroblast Growth Factor 10 / metabolism
Fibroblast Growth Factor 10 / pharmacology
Fibroblast Growth Factor 10 / therapeutic use
Humans
Inflammation / metabolism
Leukocytes, Mononuclear / metabolism
Leukocytes, Mononuclear / pathology
Lung / metabolism
Mice
Mice, Inbred BALB C
NF-kappa B* / metabolism
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism

Substances

Cytokines
FGF10 protein, human
Fibroblast Growth Factor 10
NF-kappa B
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
Fgf10 protein, mouse