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Sci Rep. 2018 Nov 6;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.

Author information

1
Department of Pathobiology, University of Guelph, 50 Stone Road East, Guelph, Ontario, N1G 2W1, Canada.
2
BenchSci, 559 College St, Toronto, ON, M6G 1A9, Canada.
3
BioAssay Works LLC, 10075 Tyler Place, Suite 18, Ijamsville, MD, 21754, USA.
4
Department of Clinical Studies, University of Guelph, 50 Stone Road East, Guelph, Ontario, N1G 2W1, Canada.
5
Asia Pacific Centre for Animal Health (APCAH), Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Victoria, 3010, Australia.
6
Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Im Neuenheimer Feld 282, 69120, Heidelberg, Germany.
7
Department of Pathobiology, University of Guelph, 50 Stone Road East, Guelph, Ontario, N1G 2W1, Canada. dbienzle@uoguelph.ca.

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.

PMID:
30401798
PMCID:
PMC6219531
DOI:
10.1038/s41598-018-34636-9
[Indexed for MEDLINE]
Free PMC Article

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