Dataset Information

Gene expression analysis reveals immune and metabolic candidate pathways in the pathogenesis of chronic otitis media.

ABSTRACT:

Objectives

Chronic otitis media (COM) is a common disease and causes significant hearing impairment in many adults. Our study aimed to investigate the immune response in COM adult patients through RNA sequencing.

Methods

In this study, we enrolled four adult COM patients and five healthy controls (HCs) to analyze and compare the mRNA signatures in their peripheral blood mononuclear cells (PBMCs). Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed on the differentially expressed genes between the COM patients and the HCs. Furthermore, the immune cell proportions of the two groups were estimated by CIBERSORT. The GSE125532, GSE27990, and GSE23140 gene expression profiles were also retrieved and analyzed for comparison with our results.

Results

Many immune pathways and genes were upregulated in the COM patients, including the IL-17 pathway and NLRP3. Monocytes and macrophages increased (P=0.005 and P=0.033, respectively), and the CD8+ T cells decreased (P=0.033) in the COM patients compared to the HCs. The COM patients' signatures also reflected a hypoxic state.

Conclusions

Our findings emphasized the roles of several immune pathways and a hypoxic state in interpreting host responses during COM, and may enable the development of novel therapeutic tools for the disease.

SUBMITTER: Lin S

PROVIDER: S-EPMC8829611 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Gene expression analysis reveals immune and metabolic candidate pathways in the pathogenesis of chronic otitis media.

Lin Siran S Zhang Wei W Xu Yuzhen Y Liu Qianqian Q Zhang Wenhong W Shao Lingyun L

American journal of translational research 20220115 1

<h4>Objectives</h4>Chronic otitis media (COM) is a common disease and causes significant hearing impairment in many adults. Our study aimed to investigate the immune response in COM adult patients through RNA sequencing.<h4>Methods</h4>In this study, we enrolled four adult COM patients and five healthy controls (HCs) to analyze and compare the mRNA signatures in their peripheral blood mononuclear cells (PBMCs). Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes pathw ...[more]

PMID: 35173843

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Project description: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-1? 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.

Dataset Information

Gene expression analysis reveals immune and metabolic candidate pathways in the pathogenesis of chronic otitis media.

Objectives

Methods

Results

Conclusions

Publications

Gene expression analysis reveals immune and metabolic candidate pathways in the pathogenesis of chronic otitis media.

Similar Datasets

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