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Updated: Apr 26, 2026
A Mouse Model for Pathogen-induced Chronic Inflammation at Local and Systemic Sites
Published on: August 8, 2014
A mouse model of otitis media identifies HB-EGF as a mediator of inflammation-induced mucosal proliferation
Keigo Suzukawa1, Julia Tomlin1, Kwang Pak1
1Division of Otolaryngology, University of California, San Diego School of Medicine and VA Medical Center, La Jolla, California, United States of America.
Insights
Heparin-binding-epidermal growth factor (HB-EGF) drives middle ear mucosal hyperplasia in otitis media. Targeting HB-EGF may reduce long-term complications in children.
Area of Science:
- Otolaryngology
- Pediatric Infectious Diseases
- Molecular Biology
Background:
- Otitis media is a common pediatric infection with potential long-term complications.
- Middle ear mucosal hyperplasia is a significant sequela of acute otitis media.
- Growth factors' role in mucosal hyperplasia requires further investigation for therapeutic development.
Purpose of the Study:
- To identify growth factors involved in middle ear mucosal hyperplasia during otitis media.
- To investigate the therapeutic potential of targeting these growth factors.
Main Methods:
- Whole genome gene array analysis of mRNA expression during otitis media.
- In vitro testing of candidate growth factors for epithelial growth stimulation.
- In vivo determination of protein levels and histological distribution of active factors.
Main Results:
- Seven candidate growth factors were identified with upregulated mRNA expression.
- Heparin-binding-epidermal growth factor (HB-EGF) was the only factor to induce significant mucosal epithelial hyperplasia in vitro.
- HB-EGF protein was highly expressed in vivo and produced by middle ear epithelial cells and lymphocytes.
Conclusions:
- HB-EGF plays an active role in middle ear mucosal epithelial hyperplasia during otitis media.
- Therapies targeting HB-EGF could potentially reduce mucosal growth and associated sequelae.
- This research opens avenues for novel therapeutic interventions for otitis media complications.
Objective:
Otitis media is one of the most common pediatric infections. While it is usually treated without difficulty, up to 20% of children may progress to long-term complications that include hearing loss, impaired speech and language development, academic underachievement, and irreversible disease. Hyperplasia of middle ear mucosa contributes to the sequelae of acute otitis media and is of important clinical significance. Understanding the role of growth factors in the mediation of mucosal hyperplasia could lead to the development of new therapeutic interventions for this disease and its sequelae.
Methods:
From a whole genome gene array analysis of mRNA expression during acute otitis media, we identified growth factors with expression kinetics temporally related to hyperplasia. We then tested these factors for their ability to stimulate mucosal epithelial growth in vitro, and determined protein levels and histological distribution in vivo for active factors.
Results:
From the gene array, we identified seven candidate growth factors with upregulation of mRNA expression kinetics related to mucosal hyperplasia. Of the seven, only HB-EGF (heparin-binding-epidermal growth factor) induced significant mucosal epithelial hyperplasia in vitro. Subsequent quantification of HB-EGF protein expression in vivo via Western blot analysis confirmed that the protein is highly expressed from 6 hours to 24 hours after bacterial inoculation, while immunohistochemistry revealed production by middle ear epithelial cells and infiltrating lymphocytes.
Conclusion:
Our data suggest an active role for HB-EGF in the hyperplasia of the middle ear mucosal epithelium during otitis media. These results imply that therapies targeting HB-EGF could ameliorate mucosal growth during otitis media, and thereby reduce detrimental sequelae of this childhood disease.
