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Scientific reports2018; 8(1); 16408; doi: 10.1038/s41598-018-34636-9

Gene set enrichment analysis of the bronchial epithelium implicates contribution of cell cycle and tissue repair processes in equine asthma.

Abstract: Severe equine asthma is a chronic inflammatory condition of the lower airways similar to adult-onset asthma in humans. Exacerbations are characterized by bronchial and bronchiolar neutrophilic inflammation, mucus hypersecretion and airway constriction. In this study we analyzed the gene expression response of the bronchial epithelium within groups of asthmatic and non-asthmatic animals following exposure to a dusty hay challenge. After challenge we identified 2341 and 120 differentially expressed genes in asthmatic and non-asthmatic horses, respectively. Gene set enrichment analysis of changes in gene expression after challenge identified 587 and 171 significantly enriched gene sets in asthmatic and non-asthmatic horses, respectively. Gene sets in asthmatic animals pertained, but were not limited, to cell cycle, neutrophil migration and chemotaxis, wound healing, hemostasis, coagulation, regulation of body fluid levels, and the hedgehog pathway. Furthermore, transcription factor target enrichment analysis in the asthmatic group showed that transcription factor motifs with the highest enrichment scores for up-regulated genes belonged to the E2F transcription factor family. It is postulated that engagement of hedgehog and E2F pathways in asthmatic horses promotes dysregulated cell proliferation and abnormal epithelial repair. These fundamental lesions may prevent re-establishment of homeostasis and perpetuate inflammation.
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Publication Date: 2018-11-06 PubMed ID: 30401798PubMed Central: PMC6219531DOI: 10.1038/s41598-018-34636-9Google Scholar: Lookup
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  • Non-U.S. Gov't

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 article centers on a study conducted to understand the gene expression response in asthmatic and non-asthmatic horses when exposed to dusty hay. The findings of the study illuminate the involvement of cell cycle, tissue repair processes and various gene sets in severe equine asthma.

Objective

The main aim of the research was to analyze the gene expression response in the bronchial epithelium of asthmatic and non-asthmatic horses when exposed to a dusty hay challenge. This was aimed at identifying how different genes and gene sets interact and contribute to severe equine asthma.

Methodology

  • The researchers exposed groups of asthmatic and non-asthmatic horses to a dusty hay challenge.
  • Post-challenge, the gene expression response of the bronchial epithelium was observed.
  • From the data collected, differentially expressed genes were identified in both the asthmatic and non-asthmatic animals.
  • Gene set enrichment analysis was then carried out to identify significantly enriched gene sets in both groups of horses.

Findings

  • The study found a larger number of differentially expressed genes in asthmatic horses (2341) as compared to non-asthmatic horses (120).
  • 587 gene sets were significantly enriched in asthmatic horses while 171 were significantly enriched in non-asthmatic horses.
  • Gene sets in asthmatic animals pertained to various biological processes and pathways, including the cell cycle, neutrophil migration, wound healing, and the hedgehog pathway.
  • The transcription factor target enrichment analysis highlighted the E2F transcription factor family as having the highest enrichment scores for up-regulated genes in asthmatic horses.

Conclusion

It can be inferred from the study that the engagement of the hedgehog and E2F pathways in asthmatic horses promotes abnormal cell proliferation and epithelial repair. The abnormalities in these fundamental lesions possibly prevent the re-establishment of homeostasis and perpetuate inflammation, contributing to the condition of severe equine asthma. This new insight into equine asthma might prove useful in formulating future treatment strategies for the ailment.

Cite This Article

APA
Tessier L, Côté O, Clark ME, Viel L, Diaz-Méndez A, Anders S, Bienzle D. (2018). Gene set enrichment analysis of the bronchial epithelium implicates contribution of cell cycle and tissue repair processes in equine asthma. Sci Rep, 8(1), 16408. https://doi.org/10.1038/s41598-018-34636-9

Publication

Scientific reports
ISSN: 2045-2322
NlmUniqueID: 101563288
Country: England
Language: English
Volume: 8
Issue: 1
Pages: 16408

Researcher Affiliations

Tessier, Laurence
  • Department of Pathobiology, University of Guelph, 50 Stone Road East, Guelph, Ontario, N1G 2W1, Canada.
  • BenchSci, 559 College St, Toronto, ON, M6G 1A9, Canada.
Côté, Olivier
  • Department of Pathobiology, University of Guelph, 50 Stone Road East, Guelph, Ontario, N1G 2W1, Canada.
  • 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, Ontario, N1G 2W1, Canada.
Viel, Laurent
  • Department of Clinical Studies, University of Guelph, 50 Stone Road East, Guelph, Ontario, N1G 2W1, Canada.
Diaz-Méndez, Andrés
  • Department of Clinical Studies, University of Guelph, 50 Stone Road East, Guelph, Ontario, N1G 2W1, Canada.
  • Asia Pacific Centre for Animal Health (APCAH), Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Victoria, 3010, Australia.
Anders, Simon
  • Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Im Neuenheimer Feld 282, 69120, Heidelberg, Germany.
Bienzle, Dorothee
  • Department of Pathobiology, University of Guelph, 50 Stone Road East, Guelph, Ontario, N1G 2W1, Canada. dbienzle@uoguelph.ca.

MeSH Terms

  • Animals
  • Asthma / genetics
  • Asthma / pathology
  • Bronchi / pathology
  • Cell Cycle / genetics
  • Cell Movement / genetics
  • Gene Expression Profiling
  • Hedgehog Proteins / metabolism
  • Homeostasis / genetics
  • Horses
  • Neutrophils / cytology
  • Respiratory Mucosa / metabolism
  • Sequence Analysis, RNA

Conflict of Interest Statement

The authors declare no competing interests.

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