The effects of chronic <i>Aspergillus fumigatus</i> exposure on the expression of platelet-derived growth factor and airway remodeling in the asthmatic rats_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

SUN Huimin ¹ , ZHANG Lingxuan ¹ , SONG Ge ¹ ,  GAO Fusheng ²

1. Clinical Medical College, Shandong Second Medical University, Weifang, Shandong 261000, P. R. China;
2. Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Shandong Second Medical University Weifang, Shandong 261000, P. R. China;

Corresponding?author：

GAO Fusheng, Email: gaofs888@163.com

Keywords：

Aspergillus fumigatus exposure; bronchial asthma; platelet-derived growth factor (PDGF); airway remodeling

DOI：

10.7507/1671-6205.202505045

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the effects of chronic Aspergillus fumigatus (AF) exposure on the expression of platelet-derived growth factor (PDGF) and airway remodeling in the asthmatic rats. Methods Forty male Wistar rats were randomly divided into five groups (8 rats per group): group A (control group): sensitized with ovalbumin (OVA) and challenged with saline; group B (bronchial asthma group): sensitized and challenged with OVA to establish a chronic asthma model; groups C-E (bronchial chronic asthma + AF spores inhalation for 1 week, 3 weeks, or 5 weeks): the asthma rats were received intranasal inhalation of Aspergillus fumigatus spores for 1 week (Group C), 3 weeks (Group D), or 5 weeks (Group E). The concentrations of interleukin-5 (IL-5), interleukin-13 (IL-13), and transforming growth factor-beta (TGF-β) in bronchoalveolar lavage fluid (BALF) were measured using enzyme-linked immunosorbent assay (ELISA). Lung sections were stained with periodic acid Schiff (PAS) and Masson trichrome stain, and the images were analyzed morphometrically.The expression of PDGF were detected by immunohistochemistry and Western blot. Results The levels of TGF-β (66.43 ± 2.78 ng/mL), IL-5 (33.49 ± 2.01 ng/mL), and IL-13 (50.78 ± 2.16 ng/mL) in BALF, as well as the extent of goblet cell hyperplasia (8.82 ± 1.95) and the degree of subepithelial collagen deposition (10.28 ± 2.48) in group B were higher than those in Group A (P<0.05). After inhalation of AF spores, the concentrations of TGF-β, IL-5, IL-13, along with the extent of goblet cell hyperplasia, and the degree of collagen deposition in the airways were increased progressively in group C, group D and group E (P<0.05). The expression of PDGF in the airways were upregulated in a dose-dependent manner. The extent of subepithelial collagen deposition and goblet cell hyperplasia in the airways were positively correlated with the expression of PDGF. Conclusion Chronic exposure to Aspergillus fumigatus upregulates the expression of PDGF in the airways of bronchial asthma rats, thereby promoting airway remodeling.

Citation： SUN Huimin, ZHANG Lingxuan, SONG Ge, GAO Fusheng. The effects of chronic Aspergillus fumigatus exposure on the expression of platelet-derived growth factor and airway remodeling in the asthmatic rats. Chinese Journal of Respiratory and Critical Care Medicine, 2025, 24(12): 872-878. doi: 10.7507/1671-6205.202505045 Copy

1.	Sockrider M, Fussner L. What Is Asthma? Am J Respir Crit Care Med, 2020, 202(9): P25-P26.
2.	Tiotiu A, Steiropoulos P, Novakova S, et al. Airway Remodeling in Asthma: Mechanisms, Diagnosis, Treatment, and Future Directions. Arch Bronconeumol, 2025, 61(1): 31-40.
3.	Tiwary M, Samarasinghe AE. Initiation and Pathogenesis of Severe Asthma with Fungal Sensitization. Cells, 2021, 10(4): 913.
4.	Agarwal R, Muthu V, Sehgal IS. Relationship between Aspergillus and asthma. Allergol Int. 2023, 72(4): 507-520.
5.	Van de Veerdonk FL, Gresnigt MS, Romani L, et al. Aspergillus fumigatus morphology and dynamic host interactions. Nat Rev Microbiol, 2017, 15(11): 661-674.
6.	Fredriksson L, Li H, Eriksson U. The PDGF family: four gene products form five dimeric isoforms. Cytokine Growth Factor Rev, 2004, 15(4): 197-204.
7.	Kardas G, Daszyńska-Kardas A, Marynowski M, et al. Role of Platelet-Derived Growth Factor (PDGF) in Asthma as an Immunoregulatory Factor Mediating Airway Remodeling and Possible Pharmacological Target. Front Pharmacol, 2020, 11(2): 1-9.
8.	Yamashita N, Sekine K, Miyasaka T, et al. Platelet-derived growth factor is involved in the augmentation of airway responsiveness through remodeling of airways in diesel exhaust particulate-treated mice. J Allergy Clin Immunol, 2001, 107(1): 135-142.
9.	Hirota JA, Ask K, Farkas L, et al. In vivo role of platelet-derived growth factor-BB in airway smooth muscle proliferation in mouse lung. Am J Respir Cell Mol Biol, 2011, 45(3): 566-572.
10.	Gao FS, Qiao JO, Zhang Y, et al. Chronic intranasal administration of Aspergillus fumigatus spores leads to aggravation of airway inflammation and remodelling in asthmatic rats. Respirology, 2009, 14(3): 360-370.
11.	Gao FS, Cao TM, Gao YY, et al. Effects of chronic exposure to Aspergillus fumigatus on epidermal growth factor receptor expression in the airway epithelial cells of asthmatic rats. Exp Lung Res, 2014, 40(6): 298-307.
12.	李萌, 張令軒, 宋歌, 等. 蝦青素對支氣管哮喘大鼠氣道炎癥及氣道重構的影響. 中國呼吸與危重監護雜志, 2024, 23(08): 575-582.
13.	張令軒, 李萌, 宋歌, 等. 慢性煙曲霉暴露對支氣管哮喘大鼠氣道Toll樣受體4表達的影響. 重慶醫科大學學報, 2025, 15(05): 1-8.
14.	Palmans E, Kips JC, Pauwels RA. Prolonged allergen exposure induces structural airway changes in sensitized rats. Am J Respir Crit Care Med, 2000, 161(2 Pt 1): 627-635.
15.	Fei X, Zhang X, Zhang GQ, et al. Cordycepin inhibits airway remodeling in a rat model of chronic asthma. Biomed Pharmacother, 2017, 88: 335-341.
16.	曹曉梅, 朱慧志, 楊磊, 等. 陽和平喘顆粒對哮喘大鼠HMGB1相關信號通路蛋白及炎癥因子的影響. 中國中西醫結合雜志, 2023, 43(06): 712-721.
17.	Denis O, van den Br?le S, Heymans J, et al. Chronic intranasal administration of mould spores or extracts to unsensitized mice leads to lung allergic inflammation, hyper-reactivity and remodelling. Immunology, 2007, 122(2): 268-278.
18.	Stern J, Pier J, Litonjua AA. Asthma epidemiology and risk factors. Semin Immunopathol, 2020, 42(1): 5-15.
19.	Dales RE, Cakmak S, Judek S, et al. The role of fungal spores in thunderstorm asthma. Chest, 2003, 123(3): 745-750.
20.	Engelhart S, Hanfland J, Glasmacher A, et al. Impact of portable air filtration units on exposure of haematology-oncology patients to airborne Aspergillus fumigatus spores under field conditions. J Hosp Infect, 2003, 54(4): 300-304.
21.	Raby KL, Michaeloudes C, Tonkin J, et al. Mechanisms of airway epithelial injury and abnormal repair in asthma and COPD. Front Immunol, 2023, 14: 1201658.
22.	Banno A, Reddy AT, Lakshmi SP, et al. Bidirectional interaction of airway epithelial remodeling and inflammation in asthma. Clin Sci (Lond), 2020, 134(9): 1063-1065.
23.	Bazan-Socha S, Buregwa-Czuma S, Jakiela B, et al. Reticular Basement Membrane Thickness Is Associated with Growth and Fibrosis-Promoting Airway Transcriptome Profile-Study in Asthma Patients. Int J Mol Sci, 2021, 22(3): 998.
24.	Gour N, Wills-Karp M. IL-4 and IL-13 signaling in allergic airway disease. Cytokine, 2015, 75(1): 68-78.
25.	Hogaboam CM, Blease K, Mehrad B, et al. Chronic airway hyperreactivity, goblet cell hyperplasia, and peribronchial fibrosis during allergic airway disease induced by Aspergillus fumigatus. Am J Pathol, 2000, 156(2): 723-32.
26.	Heldin CH, Lennartsson J. Structural and functional properties of platelet-derived growth factor and stem cell factor receptors. Cold Spring Harb Perspect Biol, 2013, 5(8): 1-19.
27.	Heldin CH, Westermark B. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev, 1999, 79(4): 1283-1316.
28.	Zhang Y, Yao F, Qin Z. JNJ0966 inhibits PDGF-BB-induced airway smooth muscle cell proliferation and extracellular matrix production by regulating MMP-9. Allergol Immunopathol (Madr), 2022, 50(4): 57-63.
29.	Kong Y, Ding L, Xu Y, et al. YiQi GuBen Formula Inhibits PDGF-BB-Induced Proliferation and Migration of Airway Smooth Muscle Cells. Pharmacology, 2020, 105(7-8): 424-433.
30.	Spinelli AM, González-Cobos JC, Zhang X, et al. Airway smooth muscle STIM1 and Orai1 are upregulated in asthmatic mice and mediate PDGF-activated SOCE, CRAC currents, proliferation, and migration. Pflugers Arch, 2012, 464(5): 481-492.
31.	Wang H, Zhong B, Geng Y, et al. TIPE2 inhibits PDGF-BB-induced phenotype switching in airway smooth muscle cells through the PI3K/Akt signaling pathway. Respir Res, 2021, 22(1): 1-12.
32.	Liu HB, Bai J, Wang WX. CST1 promotes the proliferation and migration of PDGF-BB-treated airway smooth muscle cells via the PI3K/AKT signaling pathway. Kaohsiung J Med Sci, 2023, 39(2): 145-153.
33.	Li Z, Zhu S. STOML2 knockdown inhibits inflammation and airway remodeling of PDGF-BB-induced airway smooth-muscle cells by the MAPK pathway. J Asthma, 2025, 8(20): 1-20.
34.	Li J, Wang X, Su Y, et al. TRIM33 Modulates Inflammation and Airway Remodeling of PDGF-BB-Induced Airway Smooth-Muscle Cells by the Wnt/β-Catenin Pathway. Int Arch Allergy Immunol, 2022, 183(10): 1127-1136.

1. Sockrider M, Fussner L. What Is Asthma? Am J Respir Crit Care Med, 2020, 202(9): P25-P26.
2. Tiotiu A, Steiropoulos P, Novakova S, et al. Airway Remodeling in Asthma: Mechanisms, Diagnosis, Treatment, and Future Directions. Arch Bronconeumol, 2025, 61(1): 31-40.
3. Tiwary M, Samarasinghe AE. Initiation and Pathogenesis of Severe Asthma with Fungal Sensitization. Cells, 2021, 10(4): 913.
4. Agarwal R, Muthu V, Sehgal IS. Relationship between Aspergillus and asthma. Allergol Int. 2023, 72(4): 507-520.
5. Van de Veerdonk FL, Gresnigt MS, Romani L, et al. Aspergillus fumigatus morphology and dynamic host interactions. Nat Rev Microbiol, 2017, 15(11): 661-674.
6. Fredriksson L, Li H, Eriksson U. The PDGF family: four gene products form five dimeric isoforms. Cytokine Growth Factor Rev, 2004, 15(4): 197-204.
7. Kardas G, Daszyńska-Kardas A, Marynowski M, et al. Role of Platelet-Derived Growth Factor (PDGF) in Asthma as an Immunoregulatory Factor Mediating Airway Remodeling and Possible Pharmacological Target. Front Pharmacol, 2020, 11(2): 1-9.
8. Yamashita N, Sekine K, Miyasaka T, et al. Platelet-derived growth factor is involved in the augmentation of airway responsiveness through remodeling of airways in diesel exhaust particulate-treated mice. J Allergy Clin Immunol, 2001, 107(1): 135-142.
9. Hirota JA, Ask K, Farkas L, et al. In vivo role of platelet-derived growth factor-BB in airway smooth muscle proliferation in mouse lung. Am J Respir Cell Mol Biol, 2011, 45(3): 566-572.
10. Gao FS, Qiao JO, Zhang Y, et al. Chronic intranasal administration of Aspergillus fumigatus spores leads to aggravation of airway inflammation and remodelling in asthmatic rats. Respirology, 2009, 14(3): 360-370.
11. Gao FS, Cao TM, Gao YY, et al. Effects of chronic exposure to Aspergillus fumigatus on epidermal growth factor receptor expression in the airway epithelial cells of asthmatic rats. Exp Lung Res, 2014, 40(6): 298-307.
12. 李萌, 張令軒, 宋歌, 等. 蝦青素對支氣管哮喘大鼠氣道炎癥及氣道重構的影響. 中國呼吸與危重監護雜志, 2024, 23(08): 575-582.
13. 張令軒, 李萌, 宋歌, 等. 慢性煙曲霉暴露對支氣管哮喘大鼠氣道Toll樣受體4表達的影響. 重慶醫科大學學報, 2025, 15(05): 1-8.
14. Palmans E, Kips JC, Pauwels RA. Prolonged allergen exposure induces structural airway changes in sensitized rats. Am J Respir Crit Care Med, 2000, 161(2 Pt 1): 627-635.
15. Fei X, Zhang X, Zhang GQ, et al. Cordycepin inhibits airway remodeling in a rat model of chronic asthma. Biomed Pharmacother, 2017, 88: 335-341.
16. 曹曉梅, 朱慧志, 楊磊, 等. 陽和平喘顆粒對哮喘大鼠HMGB1相關信號通路蛋白及炎癥因子的影響. 中國中西醫結合雜志, 2023, 43(06): 712-721.
17. Denis O, van den Br?le S, Heymans J, et al. Chronic intranasal administration of mould spores or extracts to unsensitized mice leads to lung allergic inflammation, hyper-reactivity and remodelling. Immunology, 2007, 122(2): 268-278.
18. Stern J, Pier J, Litonjua AA. Asthma epidemiology and risk factors. Semin Immunopathol, 2020, 42(1): 5-15.
19. Dales RE, Cakmak S, Judek S, et al. The role of fungal spores in thunderstorm asthma. Chest, 2003, 123(3): 745-750.
20. Engelhart S, Hanfland J, Glasmacher A, et al. Impact of portable air filtration units on exposure of haematology-oncology patients to airborne Aspergillus fumigatus spores under field conditions. J Hosp Infect, 2003, 54(4): 300-304.
21. Raby KL, Michaeloudes C, Tonkin J, et al. Mechanisms of airway epithelial injury and abnormal repair in asthma and COPD. Front Immunol, 2023, 14: 1201658.
22. Banno A, Reddy AT, Lakshmi SP, et al. Bidirectional interaction of airway epithelial remodeling and inflammation in asthma. Clin Sci (Lond), 2020, 134(9): 1063-1065.
23. Bazan-Socha S, Buregwa-Czuma S, Jakiela B, et al. Reticular Basement Membrane Thickness Is Associated with Growth and Fibrosis-Promoting Airway Transcriptome Profile-Study in Asthma Patients. Int J Mol Sci, 2021, 22(3): 998.
24. Gour N, Wills-Karp M. IL-4 and IL-13 signaling in allergic airway disease. Cytokine, 2015, 75(1): 68-78.
25. Hogaboam CM, Blease K, Mehrad B, et al. Chronic airway hyperreactivity, goblet cell hyperplasia, and peribronchial fibrosis during allergic airway disease induced by Aspergillus fumigatus. Am J Pathol, 2000, 156(2): 723-32.
26. Heldin CH, Lennartsson J. Structural and functional properties of platelet-derived growth factor and stem cell factor receptors. Cold Spring Harb Perspect Biol, 2013, 5(8): 1-19.
27. Heldin CH, Westermark B. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev, 1999, 79(4): 1283-1316.
28. Zhang Y, Yao F, Qin Z. JNJ0966 inhibits PDGF-BB-induced airway smooth muscle cell proliferation and extracellular matrix production by regulating MMP-9. Allergol Immunopathol (Madr), 2022, 50(4): 57-63.
29. Kong Y, Ding L, Xu Y, et al. YiQi GuBen Formula Inhibits PDGF-BB-Induced Proliferation and Migration of Airway Smooth Muscle Cells. Pharmacology, 2020, 105(7-8): 424-433.
30. Spinelli AM, González-Cobos JC, Zhang X, et al. Airway smooth muscle STIM1 and Orai1 are upregulated in asthmatic mice and mediate PDGF-activated SOCE, CRAC currents, proliferation, and migration. Pflugers Arch, 2012, 464(5): 481-492.
31. Wang H, Zhong B, Geng Y, et al. TIPE2 inhibits PDGF-BB-induced phenotype switching in airway smooth muscle cells through the PI3K/Akt signaling pathway. Respir Res, 2021, 22(1): 1-12.
32. Liu HB, Bai J, Wang WX. CST1 promotes the proliferation and migration of PDGF-BB-treated airway smooth muscle cells via the PI3K/AKT signaling pathway. Kaohsiung J Med Sci, 2023, 39(2): 145-153.
33. Li Z, Zhu S. STOML2 knockdown inhibits inflammation and airway remodeling of PDGF-BB-induced airway smooth-muscle cells by the MAPK pathway. J Asthma, 2025, 8(20): 1-20.
34. Li J, Wang X, Su Y, et al. TRIM33 Modulates Inflammation and Airway Remodeling of PDGF-BB-Induced Airway Smooth-Muscle Cells by the Wnt/β-Catenin Pathway. Int Arch Allergy Immunol, 2022, 183(10): 1127-1136.

Chinese Journal of Respiratory and Critical Care Medicine

The effects of chronic Aspergillus fumigatus exposure on the expression of platelet-derived growth factor and airway remodeling in the asthmatic rats

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content