Related Experiment Video
Updated: Apr 30, 2026
Refined Murine Model of Idiopathic Pulmonary Fibrosis
Published on: June 17, 2025
Effect of nilotinib on airway remodeling in a murine model of chronic asthma
Chin Kook Rhee1, Ji Young Kang, Chan Kwon Park
1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Unlabelled:
ABSTRACT Objective: The tyrosine kinase inhibitor nilotinib has potent inhibitory activity against the stem cell growth factor receptor c-Kit and platelet-derived growth factor receptor (PDGFR). The present study aimed to determine whether nilotinib suppresses airway remodeling and whether its effect is associated with the c-Kit and PDGFR pathways. We also aimed to compare the effect of nilotinib and imatinib on remodeling.
Methods:
We developed a mouse model of airway remodeling, which includes smooth muscle thickening, in which ovalbumin (OVA)-sensitized mice were repeatedly exposed to intranasal OVA administration twice a week for 3 months. Mice were treated with nilotinib or imatinib during the OVA challenge.
Results:
Compared with control mice, the mice chronically exposed to OVA developed sustained eosinophilic airway inflammation, airway hyperresponsiveness (AHR), and exhibited features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Administration of nilotinib significantly inhibited eosinophilic inflammation, AHR, and remodeling in mice chronically exposed to OVA. Nilotinib showed a trend of more potent effect than imatinib on attenuating remodeling in hydroxyproline assay and smooth muscle staining. Nilotinib treatment significantly reduced the expression of phosphorylated (p)-c-Kit, p-PDGFRβ, and p-extracellular signal-regulated kinase 1/2. The expression levels of the genes encoding c-Kit and PDGFRβ were also reduced by nilotinib treatment. Treatment with nilotinib did not affect significantly the level of OVA-specific IgE and IgG1 in serum. In vitro, nilotinib significantly inhibited cell proliferation of fibroblast.
Conclusions:
These results suggest that nilotinib administration can prevent airway inflammation, AHR, and airway remodeling associated with chronic allergen challenge.
Insights
Nilotinib effectively prevents airway inflammation and remodeling in a mouse model. This tyrosine kinase inhibitor targets c-Kit and PDGFR pathways, offering a potential therapeutic strategy for allergic airway diseases.
Area of Science:
- Respiratory Medicine
- Pharmacology
- Immunology
Background:
- Airway remodeling is a key feature of chronic allergic airway diseases.
- The stem cell growth factor receptor c-Kit and platelet-derived growth factor receptor (PDGFR) pathways are implicated in airway remodeling.
Purpose of the Study:
- To investigate the effect of nilotinib on airway remodeling in a mouse model.
- To determine if nilotinib's effects are mediated through c-Kit and PDGFR pathways.
- To compare nilotinib with imatinib in suppressing airway remodeling.
Main Methods:
- A mouse model of airway remodeling was established using ovalbumin (OVA) sensitization and challenge.
- Mice were treated with nilotinib or imatinib during OVA exposure.
- Key markers of inflammation, airway hyperresponsiveness (AHR), and airway remodeling were assessed.
- In vitro fibroblast proliferation was evaluated.
Main Results:
- Nilotinib significantly inhibited eosinophilic airway inflammation, AHR, and airway remodeling.
- Nilotinib reduced the expression of phosphorylated c-Kit, PDGFRβ, and extracellular signal-regulated kinase 1/2.
- Nilotinib demonstrated a trend towards a more potent effect than imatinib on remodeling.
- Nilotinib inhibited fibroblast proliferation in vitro.
Conclusions:
- Nilotinib administration can prevent airway inflammation, AHR, and airway remodeling.
- The findings suggest nilotinib's therapeutic potential for chronic allergen-induced airway diseases.
