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PloS one2012; 7(1); e29440; doi: 10.1371/journal.pone.0029440

Profiling of differentially expressed genes using suppression subtractive hybridization in an equine model of chronic asthma.

Abstract: Gene expression analyses are used to investigate signaling pathways involved in diseases. In asthma, they have been primarily derived from the analysis of bronchial biopsies harvested from mild to moderate asthmatic subjects and controls. Due to ethical considerations, there is currently limited information on the transcriptome profile of the peripheral lung tissues in asthma. Objective: To identify genes contributing to chronic inflammation and remodeling in the peripheral lung tissue of horses with heaves, a naturally occurring asthma-like condition. Methods: Eleven adult horses (6 heaves-affected and 5 controls) were studied while horses with heaves were in clinical remission (Pasture), and during disease exacerbation induced by a 30-day natural antigen challenge during stabling (Challenge). Large peripheral lung biopsies were obtained by thoracoscopy at both time points. Using suppression subtractive hybridization (SSH), lung cDNAs of controls (Pasture and Challenge) and asymptomatic heaves-affected horses (Pasture) were subtracted from cDNAs of horses with heaves in clinical exacerbation (Challenge). The differential expression of selected genes of interest was confirmed using quantitative PCR assay. Results: Horses with heaves, but not controls, developed airway obstruction when challenged. Nine hundred and fifty cDNA clones isolated from the subtracted library were screened by dot blot array and 224 of those showing the most marked expression differences were sequenced. The gene expression pattern was confirmed by quantitative PCR in 15 of 22 selected genes. Novel genes and genes with an already defined function in asthma were identified in the subtracted cDNA library. Genes of particular interest associated with asthmatic airway inflammation and remodeling included those related to PPP3CB/NFAT, RhoA, and LTB4/GPR44 signaling pathways. Conclusions: Pathways representing new possible targets for anti-inflammatory and anti-remodeling therapies for asthma were identified. The findings of genes previously associated with asthma validate this equine model for gene expression studies.
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Publication Date: 2012-01-03 PubMed ID: 22235296PubMed Central: PMC3250435DOI: 10.1371/journal.pone.0029440Google 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 article presents a study on how gene expression analyses are used to investigate signalling pathways involved in asthma, using an equine model, with a specific focus on chronic inflammation and remodeling in the peripheral lung tissue of horses with heaves, an asthma-like condition.

Objectives and Methodology of the Study

  • The aim of the study was to identify genes contributing to chronic inflammation and remodeling in the peripheral lung tissue of horses with a condition known as heaves, an analogous condition to human asthma.
  • The researchers studied 11 adult horses, 6 of which were affected by heaves and 5 were controls. The horses were studied during clinical remission and during disease exacerbation induced by a 30-day natural antigen challenge.
  • Large peripheral lung biopsies were obtained from the horses at both time points using a procedure known as thoracoscopy.
  • A technique known as suppression subtractive hybridization (SSH) was used to compare gene expression between the control horses and the ones affected by heaves. This technique allows researchers to compare two RNA samples and identify the differences between them.
  • The differential expression of selected genes was then confirmed using a quantitative PCR assay, a common method for measuring the amount of a specific RNA.

    • Results of the Study

    • The study found that horses with heaves, but not the controls, developed airway obstruction when challenged.
    • 950 clones isolated from the subtracted library were analyzed and 224 of those showing the most significant expression differences were sequenced for further investigation.
    • The study confirmed the differential expression of 15 out of 22 selected genes using a quantitative PCR.
    • The identified genes included both novel genes and genes already associated with asthma, reinforcing the validity of the available equine model for gene expression studies in this area.
    • Particular genes associated with asthmatic airway inflammation and remodeling, relating to PPP3CB/NFAT, RhoA, and LTB4/GPR44 signaling pathways were identified.

    Conclusions and Implications

    • The study points out potential new targets for anti-inflammatory and anti-remodeling therapies for asthma, enhancing our understanding of the genetic basis of asthmatic conditions and potentially contributing to the development of new treatment strategies.
    • The identified genes could become the focus of future research and aid in gaining a better understanding of the molecular mechanisms and signaling pathways involved in asthma and similar chronic respiratory diseases.
    • The successful use of the equine model validates its application for similar gene expression studies, potentially paving the way for more extensive application in future research.

Cite This Article

APA
Lavoie JP, Lefebvre-Lavoie J, Leclere M, Lavoie-Lamoureux A, Chamberland A, Laprise C, Lussier J. (2012). Profiling of differentially expressed genes using suppression subtractive hybridization in an equine model of chronic asthma. PLoS One, 7(1), e29440. https://doi.org/10.1371/journal.pone.0029440

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 7
Issue: 1
Pages: e29440
PII: e29440

Researcher Affiliations

Lavoie, Jean-Pierre
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Q, Canada. jean-pierre.lavoie@umontreal.ca
Lefebvre-Lavoie, Josiane
    Leclere, Mathilde
      Lavoie-Lamoureux, Anouk
        Chamberland, Annie
          Laprise, Catherine
            Lussier, Jacques

              MeSH Terms

              • Animals
              • Antigens / immunology
              • Asthma / genetics
              • Chronic Disease
              • Cloning, Molecular
              • Disease Models, Animal
              • Female
              • Gene Expression Profiling / methods
              • Gene Library
              • Horses
              • Lung / immunology
              • Lung / metabolism
              • Male
              • Polymerase Chain Reaction

              Grant Funding

              • MIF79636 / Canadian Institutes of Health Research

              Conflict of Interest Statement

              The authors have declared that no competing interests exist.

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