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BMC genomics2017; 18(1); 708; doi: 10.1186/s12864-017-4107-6

Impaired response of the bronchial epithelium to inflammation characterizes severe equine asthma.

Abstract: Severe equine asthma is a naturally occurring lung inflammatory disease of mature animals characterized by neutrophilic inflammation, bronchoconstriction, mucus hypersecretion and airway remodeling. Exacerbations are triggered by inhalation of dust and microbial components. Affected animals eventually are unable of aerobic performance. In this study transcriptomic differences between asthmatic and non-asthmatic animals in the response of the bronchial epithelium to an inhaled challenge were determined. Results: Paired endobronchial biopsies were obtained pre- and post-challenge from asthmatic and non-asthmatic animals. The transcriptome, determined by RNA-seq and analyzed with edgeR, contained 111 genes differentially expressed (DE) after challenge between horses with and without asthma, and 81 of these were upregulated. Genes involved in neutrophil migration and activation were in central location in interaction networks, and related gene ontology terms were significantly overrepresented. Relative abundance of specific gene products as determined by immunohistochemistry was correlated with differential gene expression. Gene sets involved in neutrophil chemotaxis, immune and inflammatory response, secretion, blood coagulation and apoptosis were overrepresented among up-regulated genes, while the rhythmic process gene set was overrepresented among down-regulated genes. MMP1, IL8, TLR4 and MMP9 appeared to be the most important proteins in connecting the STRING protein network of DE genes. Conclusions: Several differentially expressed genes and networks in horses with asthma also contribute to human asthma, highlighting similarities between severe human adult and equine asthma. Neutrophil activation by the bronchial epithelium is suggested as the trigger of the inflammatory cascade in equine asthma, followed by epithelial injury and impaired repair and differentiation. Circadian rhythm dysregulation and the sonic Hedgehog pathway were identified as potential novel contributory factors in equine asthma.
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Publication Date: 2017-09-08 PubMed ID: 28886691PubMed Central: PMC5591550DOI: 10.1186/s12864-017-4107-6Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research study focuses on the difference in bronchial epithelium response to inflammation between healthy horses and those suffering from severe equine asthma. Using transcriptomic analysis, the study identifies several differentially expressed genes and networks that are similar to those found in human asthma. The study suggests the key role of neutrophil activation as a trigger for the inflammatory response in equine asthma and highlights potential novel contributory factors like circadian rhythm dysregulation and the sonic Hedgehog pathway.

Research Methodology

  • The study used endobronchial biopsies obtained from both asthmatic and non-asthmatic horses, before and after an inhaled challenge.
  • The transcriptome of the biopsies was determined through RNA sequencing, and the data was analyzed with edgeR, a bioconductor software package for differential expression analysis.
  • The research identified 111 differentially expressed genes after the challenge between horses with and without asthma. Of these, 81 genes were upregulated.
  • Immunohistochemistry was employed to correlate the relative abundance of specific gene products with differential gene expression.

Research Findings

  • The study identified the genes involved in neutrophil migration and activation to be central in interaction networks. These related gene ontology terms were significantly overrepresented, suggesting the key role of neutrophil activation in the inflammatory response in equine asthma.
  • Gene sets involved in neutrophil chemotaxis, immune and inflammatory response, secretion, blood coagulation and apoptosis were overrepresented among up-regulated genes, indicating these processes were elevated in asthmatic horses.
  • Interestingly, the study found that the rhythmic process gene set was overrepresented among down-regulated genes, hinting at potential dysregulation of circadian rhythms in asthmatic horses.
  • Key proteins connecting the differentially expressed gene network included MMP1, IL8, TLR4 and MMP9. These are known contributors to inflammatory responses, highlighting their importance in the asthma pathway.

Conclusions and Implications

  • The study revealed several differentially expressed genes and interconnecting networks contributing to equine asthma that are also present in human asthma. This highlights the similarities between human adult asthma and severe equine asthma, potentially informing future medical research.
  • The impairments in bronchial epithelium response to inflammation in asthmatic horses were identified, suggesting epithelial injury and impaired repair and differentiation as part of the disease progression.
  • The study also identified potential new contributory factors to equine asthma, like circadian rhythm dysregulation and the sonic Hedgehog pathway. These novel findings show potential directions for future research into equine asthma.

Cite This Article

APA
Tessier L, Côté O, Clark ME, Viel L, Diaz-Méndez A, Anders S, Bienzle D. (2017). Impaired response of the bronchial epithelium to inflammation characterizes severe equine asthma. BMC Genomics, 18(1), 708. https://doi.org/10.1186/s12864-017-4107-6

Publication

BMC genomics
ISSN: 1471-2164
NlmUniqueID: 100965258
Country: England
Language: English
Volume: 18
Issue: 1
Pages: 708
PII: 708

Researcher Affiliations

Tessier, Laurence
  • Department of Pathobiology, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada.
Côté, Olivier
  • Department of Pathobiology, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada.
  • Present address: BioAssay Works LLC, 10075 Tyler Place, Suite 18, Ijamsville, MD, 21754, USA.
Clark, Mary Ellen
  • Department of Pathobiology, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada.
Viel, Laurent
  • Department of Clinical Studies, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada.
Diaz-Méndez, Andrés
  • Department of Clinical Studies, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada.
  • Present address: Centre for Equine Infectious Disease, The University of Melbourne, Melbourne, VIC, 3010, Australia.
Anders, Simon
  • Institute for Molecular Medicine, Finland (FIMM), University of Helsinki, Tukholmankatu 8, 00014, Helsinki, Finland.
Bienzle, Dorothee
  • Department of Pathobiology, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada. dbienzle@uoguelph.ca.

MeSH Terms

  • Animals
  • Asthma / genetics
  • Bronchi / metabolism
  • Gene Expression Profiling
  • Gene Ontology
  • Horses
  • Inflammation / genetics
  • Respiratory Mucosa / metabolism

Conflict of Interest Statement

ETHICS APPROVAL: All procedures were approved by the Institutional Animal Care Committee of the University of Guelph (protocol R10–031) and conducted in compliance with Canadian Council on Animal Care guidelines. Animals used in this research belong to the University of Guelph. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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