Investigating the Relationship between FGF2 Gene Expression and Airway Remodeling in Severe Asthma
Abstract
Severe asthma causes chronic airway inflammation and structural changes in the bronchial wall. Fibroblast growth factor 2 (FGF2) plays an inflammatory role in specific pathways in airway remodeling in asthma. Assessing the relationship between sputum pattern, bronchial thickness by high-resolution computed tomography (HRCT) scan, and FGF2 expression level can evaluate the role of FGF2 in asthma remodeling.
The study aimed to investigate the correlation between airway wall thickness and FGF2 gene expression in 100 participants with severe asthma. The method involved measuring airway wall thickness using HRCT and analyzing FGF2 gene expression through real-time reverse transcriptase polymerase chain reaction. The participants were divided into 2 groups based on bronchodilator responsiveness and classified into different asthma phenotypes based on sputum cell count.
The baseline data did not show a significant difference between the groups. The study found significant differences in airway variables between different asthma subgroups. FGF2 expression was associated with various characteristics of asthma, including body mass index, forced expiratory volume in 1 second (FEV1), and airway wall thickness. The receiver operating characteristic curve analysis showed that a fold change higher than 2.42 in FGF2 expression indicated asthma.
Based on our research, FGF2 may play a critical role in airway thickness regardless of inflammation. We found increased FGF2 levels with disease severity and wall thickness in atopic severe persistent asthma patients with FEV1 below 60%. Further research is needed to understand FGF2's role across broader FEV1 ranges and other phenotypes.
2. Bergeron C, Tulic MK, Hamid Q. Airway remodelling in asthma: from benchside to clinical practice. Can Respir J. 2010;17(4):e85-93.
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.
4. Tan Y, Qiao Y, Chen Z, Liu J, Guo Y, Tran T, et al. FGF2, an Immunomodulatory Factor in Asthma and Chronic Obstructive Pulmonary Disease (COPD). Front Cell Dev Biol. 2020;8:223.
5. Zhang S, Smartt H, Holgate ST, Roche WR. Growth factors secreted by bronchial epithelial cells control myofibroblast proliferation: an in vitro co-culture model of airway remodeling in asthma. Lab Invest. 1999;79(4):395-405.
6. O'Sullivan MJ, Jang JH, Panariti A, Bedrat A, Ijpma G, Lemos B, et al. Airway Epithelial Cells Drive Airway Smooth Muscle Cell Phenotype Switching to the Proliferative and Pro-inflammatory Phenotype. Front Physiol. 2021;12:687654.
7. Yang L, Zhou F, Zheng D, Wang D, Li X, Zhao C, et al. FGF/FGFR signaling: From lung development to respiratory diseases. Cytokine Growth Factor Rev. 2021;62:94-104.
8. Chae EJ, Kim TB, Cho YS, Park CS, Seo JB, Kim N, et al. Airway Measurement for Airway Remodeling Defined by Post-Bronchodilator FEV1/FVC in Asthma: Investigation Using Inspiration-Expiration Computed Tomography. Allergy Asthma Immunol Res. 2011;3(2):111-7.
9. Gono H, Fujimoto K, Kawakami S, Kubo K. Evaluation of airway wall thickness and air trapping by HRCT in asymptomatic asthma. Eur Respir J. 2003;22(6):965-71.
10. Janson C, Malinovschi A, Amaral AFS, Accordini S, Bousquet J, Buist AS, et al. Bronchodilator reversibility in asthma and COPD: findings from three large population studies. Eur Respir J. 2019;54(3).
11. Manafi Varkiani M, Mirsadraee M, Anhaee Nasseri Z, Khakzad M, Ghaffari S, Rabbani Nia T. Comparison of the effects of itraconazole and prednisolone on fibroblast growth factor-2 gene expression and clinical manifestations in patients with persistent severe asthma. Curr Med Mycol. 2023;9(2):1-9.
12. Khorasani AM, Mohammadi B, Saghafi MR, Mohammadi S, Ghaffari S, Mirsadraee M, et al. The association between MUC5AC and MUC5B genes expression and remodeling progression in severe neutrophilic asthma: A direct relationship. Respir Med.2023;213:107260.
13. Bissonnette É Y, Madore AM, Chakir J, Laviolette M, Boulet LP, Hamid Q, et al. Fibroblast growth factor-2 is a sputum remodeling biomarker of severe asthma. J Asthma. 2014;51(2):119-26.
14. Cianchetti S, Cardini C, Puxeddu I, Latorre M, Bartoli ML, Bradicich M, et al. Distinct profile of inflammatory and remodelling biomarkers in sputum of severe asthmatic patients with or without persistent airway obstruction. World Allergy Organ J. 2019;12(11):100078.
15. Hao RH, Guo Y, Dong SS, Weng GZ, Yan H, Zhu DL, et al. Associations of Plasma FGF2 Levels and Polymorphisms in the FGF2 Gene with Obesity Phenotypes in Han Chinese Population. Sci Rep. 2016;6:19868.
16. Bossé Y, Rola-Pleszczynski M. FGF2 in asthmatic airway-smooth-muscle-cell hyperplasia. Trends in Molecular Medicine. 2008;14(1):3-11.
17. Guzy RD, Stoilov I, Elton TJ, Mecham RP, Ornitz DM. Fibroblast growth factor 2 is required for epithelial recovery, but not for pulmonary fibrosis, in response to bleomycin. Am J Respir Cell Mol Biol. 2015;52(1):116-28.
18. Schuliga M, Javeed A, Harris T, Xia Y, Qin C, Wang Z, et al. Transforming growth factor-β-induced differentiation of airway smooth muscle cells is inhibited by fibroblast growth factor-2. Am J Respir Cell Mol Biol. 2013;48(3):346-53.
Files | ||
Issue | Articles in Press | |
Section | Original Article(s) | |
Keywords | ||
Asthma Airway remodeling Fibroblast growth factor 2 High-resolution computed tomography |
Rights and permissions | |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |