ArticlePLoS genetics2011
HIF-VEGF pathways are critical for chronic otitis media in Junbo and Jeff mouse mutants.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 63 citations in OpenAlex.
- Radiotherapy-Induced Otitis Media With Effusion in Nasopharyngeal Carcinoma: A Meta-Analysis.The Laryngoscope · 2026Pooled it
- Dysregulation of immune response in otitis media.Expert reviews in molecular medicine · 2021Pooled it
- Challenges in functional hydrogel application for chronic tympanic membrane perforation: practical limitations and lessons learned.Biomedical engineering letters · 2026Article
- Trans-cortical vessels in the mouse temporal bulla bone are a means to recruit myeloid cells in chronic otitis media and limit peripheral leukogram changes.Frontiers in genetics · 2022Article
- Effect of Angiogenesis and Lymphangiogenesis in Diesel Exhaust Particles Inhalation in Mouse Model of LPS Induced Acute Otitis Media.Frontiers in cellular and infection microbiology · 2022Article
- Hearing Loss in Id1Frontiers in genetics · 2021Article
- Cytological and microbiological characteristics of middle ear effusions in brachycephalic dogs.Journal of veterinary internal medicine · 2020Article
- Genomics of Otitis Media (OM): Molecular Genetics Approaches to Characterize Disease Pathophysiology.Frontiers in genetics · 2020Review
- Reviewing the Pathogenic Potential of the Otitis-Associated BacteriaFrontiers in cellular and infection microbiology · 2020Review
- Effect of vascular endothelial growth factor and its receptors in adult otitis media with effusion.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2019Article
- Chronic otitis media is initiated by a bulla cavitation defect in the FBXO11 mouse model.Disease models & mechanisms · 2019Article
- Current Understanding of Host Genetics of Otitis Media.Frontiers in genetics · 2019Review
- Transcript Analysis Reveals a Hypoxic Inflammatory Environment in Human Chronic Otitis Media With Effusion.Frontiers in genetics · 2019Article
- Cellular content plays a crucial role in Non-typeable Haemophilus influenzae infection of preinflamed Junbo mouse middle ear.Cellular microbiology · 2019Article
- Loss of the homeostatic protein BPIFA1, leads to exacerbation of otitis media severity in the Junbo mouse model.Scientific reports · 2018Article
- Cognitive Decline, Dementia, Alzheimer's Disease and Presbycusis: Examination of the Possible Molecular Mechanism.Frontiers in neuroscience · 2018Review
- Understanding the aetiology and resolution of chronic otitis media from animal and human studies.Disease models & mechanisms · 2017Review
- A mouse-to-man candidate gene study identifies association of chronic otitis media with the loci TGIF1 and FBXO11.Scientific reports · 2017Article
- A mutation in Nischarin causes otitis media via LIMK1 and NF-κB pathways.PLoS genetics · 2017Article
- 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
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Otitis media with effusion (OME) is the commonest cause of hearing loss in children, yet the underlying genetic pathways and mechanisms involved are incompletely understood. Ventilation of the middle ear with tympanostomy tubes is the commonest surgical procedure in children and the best treatment for chronic OME, but the mechanism by which they work remains uncertain. As hypoxia is a common feature of inflamed microenvironments, moderation of hypoxia may be a significant contributory mechanism. We have investigated the occurrence of hypoxia and hypoxia-inducible factor (HIF) mediated responses in Junbo and Jeff mouse mutant models, which develop spontaneous chronic otitis media. We found that Jeff and Junbo mice labeled in vivo with pimonidazole showed cellular hypoxia in inflammatory cells in the bulla lumen, and in Junbo the middle ear mucosa was also hypoxic. The bulla fluid inflammatory cell numbers were greater and the upregulation of inflammatory gene networks were more pronounced in Junbo than Jeff. Hif-1α gene expression was elevated in bulla fluid inflammatory cells, and there was upregulation of its target genes including Vegfa in Junbo and Jeff. We therefore investigated the effects in Junbo of small-molecule inhibitors of VEGFR signaling (PTK787, SU-11248, and BAY 43-9006) and destabilizing HIF by inhibiting its chaperone HSP90 with 17-DMAG. We found that both classes of inhibitor significantly reduced hearing loss and the occurrence of bulla fluid and that VEGFR inhibitors moderated angiogenesis and lymphangiogenesis in the inflamed middle ear mucosa. The effectiveness of HSP90 and VEGFR signaling inhibitors in suppressing OM in the Junbo model implicates HIF-mediated VEGF as playing a pivotal role in OM pathogenesis. Our analysis of the Junbo and Jeff mutants highlights the role of hypoxia and HIF-mediated pathways, and we conclude that targeting molecules in HIF-VEGF signaling pathways has therapeutic potential in the treatment of chronic OM.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.