Journal of Shandong University (Health Sciences) ›› 2023, Vol. 61 ›› Issue (6): 1-9.doi: 10.6040/j.issn.1671-7554.0.2022.1201

• 基础医学 •    

Mechanism of FOXM1 in acute exacerbation of asthma induced by respiratory virus infection in mice

BU Meiling1,2, WANG Jinrong1, FENG Mei3, SUN Lifeng1   

  1. 1. Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China;
    2. The Second Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong, China;
    3. Central Laboratory of Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China
  • Published:2023-06-06

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Abstract: Objective To investigate the role of FOXM1 in respiratory virus-induced asthmatic attacks in mice. Methods BALB/c female mice(aged 6-8 weeks)were randomly divided into control group, asthma model group, Poly(I:C)group, RCM1+Poly(I:C)group and Poly(I:C)+RCM1 group, with 15 mice in each group. Asthma was induced in mice via nasal administration of house dust mite(HDM)and viral analogue, Poly(I:C). The FOXM1 inhibitor RCM1 was used to investigate the role of FOXM1 in virus-induced asthmatic attacks. The lung tissue and bronchial alveolar lavage fluid(BALF)were collected. The induction of asthma was determined by measuring the airway stenosis index. The expressions of IL-4, IL-13, IFN-γ, FOXM1 and MUC5AC in lung tissue and BALF were detected with real-time PCR(RT-PCR)and ELISA. The cell counts in BALF were determined with flow cytometry. The morphological changes of lung tissue and airway epithelial cells were observed with haematoxylin & eosin(HE)staining. The expressions of FOXM1 and MUC5AC were determined with immunohistochemistry. Results The airway resistance was significantly higher in asthma model group mice than in the control group(P<0.05), and Poly(I:C)administration further increased airway resistance(P<0.05). The IL-4 and IL-13 levels were as follows: control groupP<0.05). The IFN-γ level was as follows: control model>asthma model group>Poly(I:C)group(P<0.05). The administration of RCM1, before or after the administration of Poly(I:C), reversed the cytokine levels(P<0.05). The levels of FOXM1 and MUC5AC were as follows: control groupP<0.05). The administration of RCM1 further decreased the expressions of FOXM1 and MUC5AC(P<0.05). The FOXM1 expression was higher, while MUC5AC expression was lower in RCM1+Poly(I:C)group than those observed in Poly(I:C)+RCM1 group(P<0.05). In the lungs of asthmatic mice, the epithelium was thickened, the cells were disorderly arranged, infiltration of the inflammatory cells was observed, and the protein levels of FOXM1 and MUC5AC were high(P<0.05). After administering Poly(I:C), the histological changes were aggravated, and protein expression was further elevated(P<0.05). The administration of RCM1 reversed the histological changes and FOXM1 and MUC5AC levels in RCM1+Poly(I:C)and Poly(I:C)+RCM1 groups(P<0.05). Conclusion Respiratory virus in mice induces airway goblet cell hyperplasia, increases mucus secretion, promotes the expression of the inflammatory cytokines, and increases airway resistance via the FOXM1 pathway and thus leading to asthmatic attacks.

Key words: Forkhead box M1, Virus, Asthma, Airway inflammation, Goblet cell hyperplasia

CLC Number: 

  • R725.6
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