ArticlePloS one2014
A mouse model of otitis media identifies HB-EGF as a mediator of inflammation-induced mucosal proliferation.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- The ECRG4 cleavage product augurin binds the endotoxin receptor and influences the innate immune response during otitis media.Frontiers in genetics · 2022Article
- HB-EGF Plays a Pivotal Role in Mucosal Hyperplasia During Otitis Media Induced by a Viral Analog.Frontiers in cellular and infection microbiology · 2022Article
- Mitochondrial Damage and Necroptosis in Aging Cochlea.International journal of molecular sciences · 2020Article
- Human vascular endothelial cells express epithelial growth factor in response to infection by Bartonella bacilliformis.PLoS neglected tropical diseases · 2020Article
- Panel 3: Genomics, precision medicine and targeted therapies.International journal of pediatric otorhinolaryngology · 2020Review
- Role of the PI3K/AKT pathway and PTEN in otitis media.Experimental cell research · 2020Article
- Genomics of Otitis Media (OM): Molecular Genetics Approaches to Characterize Disease Pathophysiology.Frontiers in genetics · 2020Review
- A kinase inhibitor screen identifies signaling pathways regulating mucosal growth during otitis media.PloS one · 2020Article
- Lack of the hyaluronan receptor CD44 affects the course of bacterial otitis media and reduces leukocyte recruitment to the middle ear.BMC immunology · 2019Article
- Panel 3: Genetics and Precision Medicine of Otitis Media.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2017Review
- Both canonical and non-canonical NF-κB activation contribute to the proliferative response of the middle ear mucosa during bacterial infection.Innate immunity · 2016Article
- No systemic exposure of transtympanic heparin-binding epidermal growth factor like growth factor.Drug and chemical toxicology · 2016Article
- Otitis media induced by peptidoglycan-polysaccharide (PGPS) in TLR2-deficient (Tlr2(-/-)) mice for developing drug therapy.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2015Article
- The transcriptome of a complete episode of acute otitis media.BMC genomics · 2015Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
objectiveOtitis 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.
methodsFrom 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.
resultsFrom 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.
conclusionOur 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.
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