FGF2 is overexpressed in asthma and promotes airway inflammation through the FGFR/MAPK/NF-κB pathway in airway epithelial cells

Yuan-Yang Tan; Hui-Qin Zhou; Yu-Jing Lin; Liu-Tong Yi; Zhuang-Gui Chen; Qing-Dong Cao; Yan-Rong Guo; Zhao-Ni Wang; Shou-Deng Chen; Yang Li; De-Yun Wang; Yong-Kang Qiao; Yan Yan

doi:10.1186/s40779-022-00366-3

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FGF2 is overexpressed in asthma and promotes airway inflammation through the FGFR/MAPK/NF-κB pathway in airway epithelial cells

RESEARCH | Updated：2023-03-20

- FGF2 is overexpressed in asthma and promotes airway inflammation through the FGFR/MAPK/NF-κB pathway in airway epithelial cells
- FGF2 is overexpressed in asthma and promotes airway inflammation through the FGFR/MAPK/NF-κB pathway in airway epithelial cells
- 解放军医学杂志（英文版） 2022年9卷第6期页码：639-654
- Affiliations：
  
  1.Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center, the Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai 519000, Guangdong, China
  2.Department of Pathology, the Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai 519000, Guangdong, China
  3.Department of Pediatrics, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China
  4.Department of Cardiothoracic Surgery, the Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai 519000, Guangdong, China
  5.Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228, Singapore
  6.BGI-Shenzhen, Shenzhen 518083, Guangdong, China
  7.Central Laboratory, the Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai 519000, Guangdong, China
- Author bio：
  
  * qiaoyongkang@genomics.cn;
  yanyan35@mail.sysu.edu.cn
- Funds：
  
  grants awarded to YY by the National Natural Science Foundation of China(81870019;82170029);the Guangdong Provincial Natural Science Foundation(2018A030313554);the Innovation Research Team for Basic and Clinical Studies on Chronic Liver Diseases of 2018 High-Level Health Teams of Zhuhai;YKQ by the National Natural Science Foundation of China(82002612);the Chinese Postdoctoral Science Foundation(2019M660211);ZGC by the Science and Technology Program of Guangzhou, China(201704020179)
- DOI：10.1186/s40779-022-00366-3
  中图分类号：
- 纸质出版：2022-12
- Accepted：
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FGF2 is overexpressed in asthma and promotes airway inflammation through the FGFR/MAPK/NF-κB pathway in airway epithelial cells[J]. 解放军医学杂志（英文版）, 2022,9(6):639-654.

Tan YY, Zhou HQ, Lin YJ, Yi LT, Chen ZG, Cao QD, et al. FGF2 is overexpressed in asthma and promotes airway inflammation through the FGFR/MAPK/NF-κB pathway in airway epithelial cells. Mil Med Res. 2022;9(1):7.
FGF2 is overexpressed in asthma and promotes airway inflammation through the FGFR/MAPK/NF-κB pathway in airway epithelial cells[J]. 解放军医学杂志（英文版）, 2022,9(6):639-654. DOI： 10.1186/s40779-022-00366-3.

Tan YY, Zhou HQ, Lin YJ, Yi LT, Chen ZG, Cao QD, et al. FGF2 is overexpressed in asthma and promotes airway inflammation through the FGFR/MAPK/NF-κB pathway in airway epithelial cells. Mil Med Res. 2022;9(1):7. DOI： 10.1186/s40779-022-00366-3.

摘要

Abstract

Background:

Airway inflammation is the core pathological process of asthma

with the key inflammatory regulators incompletely defined. Recently

fibroblast growth factor 2 (FGF2) has been reported to be an inflammatory regulator; however

its role in asthma remains elusive. This study aimed to investigate the immunomodulatory role of FGF2 in asthma.

Methods:

First

FGF2 expression was characterised in clinical asthma samples and the house dust mite (HDM)-induced mouse chronic asthma model. Second

recombinant mouse FGF2 (rm-FGF2) protein was intranasally delivered to determine the effect of FGF2 on airway inflammatory cell infiltration. Third

human airway epithelium-derived A549 cells were stimulated with either HDM or recombinant human interleukin-1β (IL-1β) protein combined with or without recombinant human FGF2. IL-1β-induced IL-6 or IL-8 release levels were determined using enzyme-linked immunosorbent assay

and the involved signalling transduction was explored

via

Western blotting.

Results:

Compared with the control groups

the FGF2 protein levels were significantly upregulated in the bronchial epithelium and alveolar areas of clinical asthma samples [(6.70±1.79)

. (16.32±2.40)

=0.0184; (11.20±2.11)

. (21.00±3.00)

=0.033

respectively] and HDM-induced asthmatic mouse lung lysates [(1.00±0.15)

. (5.14±0.42)

0.001]. Moreover

FGF2 protein abundance was positively correlated with serum total and anti-HDM IgE levels in the HDM-induced chronic asthma model (

=0.857 and 0.783

=0.0008 and 0.0043

respectively). Elevated FGF2 protein was mainly expressed in asthmatic bronchial epithelium and alveolar areas and partly co-localised with infiltrated inflammatory cell populations in HDM-induced asthmatic mice. More importantly

intranasal instillation of rm-FGF2 aggravated airway inflammatory cell infiltration [(2.45±0.09)

. (2.88±0.14)

=0.0288] and recruited more subepithelial neutrophils after HDM challenge [(110.20±29.43) cells/mm

. (238.10±42.77) cells/mm

=0.0392] without affecting serum IgE levels and Th2 cytokine transcription. In A549 cells

FGF2 was upregulated through HDM stimulation and promoted IL-1β-induced IL-6 or IL-8 release levels [up to (1.41±0.12)- or (1.44±0.14)-fold change

. IL-1β alone groups

=0.001 or 0.0344

respectively]. The pro-inflammatory effect of FGF2 is likely mediated through the fibroblast growth factor receptor (FGFR)/mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) pathway.

Conclusions:

Our findings suggest that FGF2 is a potential inflammatory modulator in asthma

which can be induced by HDM and acts through the FGFR/MAPK/NF-κB pathway in the airway epithelial cells.

关键词

Keywords

references

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