Inhaled corticosteroids modulate the (+)insert smooth muscle myosin heavy chain in the equine asthmatic airways.
Abstract: Overexpression of the (+)insert smooth muscle myosin heavy chain (SMMHC) isoform could contribute to airway bronchospasm by increasing the velocity of contraction. Whether the (+)insert isoform is present in the small airways and its expression is reversible in asthma are unknown. Objective: To determine the anatomical location and the expression kinetics of the (+)insert SMMHC isoform in airways of horses with heaves and to evaluate its modulation in response to disease status. Methods: We evaluated the (+)insert SMMHC isoform in the airways of horses with heaves during disease exacerbation and remission, and in controls. The expression kinetics of the SMMHC (+)insert was then assessed at multiple time points in two studies: first, in horses with heaves treated for a 1-year period with antigen avoidance alone, inhaled corticosteroids alone or both; second, in horses with heaves before and after a 30-day natural antigen exposure. Gene expression analysis was assessed by quantitative PCR and protein expression was confirmed by targeted mass spectrometry. Results: The (+)insert SMMHC isoform was significantly increased in central and peripheral airways, but not in the trachea of heaves-affected horses in clinical exacerbation when compared horses with heaves in remission and controls. Both corticosteroid administration and antigen avoidance led to a significant reduction of the (+)insert expression in the airways. The (+)insert SMMHC isoform was not significantly increased in airways after 1 month of antigenic re-exposure. Conclusions: The (+)insert SMMHC expression is increased throughout the bronchial tree in horses with heaves and reversible by corticosteroids administration and antigen avoidance.
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Publication Date: 2014-09-09 PubMed ID: 25205586DOI: 10.1136/thoraxjnl-2014-205572Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This article presents a study on equine asthma and how inhaled corticosteroids affect the expression of a specific muscle chain isoform. The research indicates that the presence of this muscle chain can considerably affect asthma symptoms and its expression can be controlled with the right kind of treatments.
Research Objective
- This research aimed to understand the expression dynamics and anatomical location of the specific (+)insert smooth muscle myosin heavy chain (SMMHC) isoform in horses suffering from heaves. The study also aimed to understand how this isoform reacts to different treatments, such as inhaled corticosteroids or avoidance of antigens.
Research Methodology
- The scientists examined the expression of this particular SMMHC isoform in the airways of horses with heaves during both the exacerbation and remission phases of the disease. They also observed the response in control horses.
- They proceeded to study the expression dynamics of this isoform at multiple times, in horses with heaves that were treated for a year either with antigen avoidance alone, inhaled corticosteroids alone, or both.
- Horses with heaves were studied before and after 30 days of natural antigen exposure.
- Gene expression analysis was performed using quantitative PCR and protein expression was confirmed using targeted mass spectrometry.
Research Findings
- The results indicated a significant increase in the (+)insert SMMHC isoform in the central and peripheral airways, but not in the trachea of horses suffering from heaves in a state of clinical exacerbation. This is in comparison to horses that were in the remission phase of the disease and the control group.
- Both corticosteroid administration and antigen avoidance resulted in a significant reduction in the expression of the (+)insert form in the airways.
- The (+)insert SMMHC isoform did not show a significant increase in the airways after one month of re-exposure to antigens.
Conclusions
- The study concluded that the expression of the (+)insert SMMHC isoform is higher throughout the bronchial tree in horses suffering from heaves. This expression pattern can be reversed by the administration of corticosteroids and avoidance of antigens.
Cite This Article
APA
Boivin R, Vargas A, Lefebvre-Lavoie J, Lauzon AM, Lavoie JP.
(2014).
Inhaled corticosteroids modulate the (+)insert smooth muscle myosin heavy chain in the equine asthmatic airways.
Thorax, 69(12), 1113-1119.
https://doi.org/10.1136/thoraxjnl-2014-205572 Publication
Researcher Affiliations
- Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Q, Canada.
- Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Q, Canada.
- Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Q, Canada.
- Meakins-Christie Laboratory, Department of Medicine, McGill University, Montreal, Q, Canada.
- Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Q, Canada.
MeSH Terms
- Administration, Inhalation
- Androstadienes / administration & dosage
- Androstadienes / pharmacology
- Androstadienes / therapeutic use
- Animals
- Antigens / immunology
- Asthma / drug therapy
- Asthma / immunology
- Asthma / metabolism
- Asthma / veterinary
- Bronchi / drug effects
- Bronchi / metabolism
- Bronchoalveolar Lavage Fluid / cytology
- Female
- Fluticasone
- Gene Expression Regulation / drug effects
- Gene Expression Regulation / immunology
- Glucocorticoids / administration & dosage
- Glucocorticoids / pharmacology
- Glucocorticoids / therapeutic use
- Horse Diseases / drug therapy
- Horse Diseases / metabolism
- Horses
- Male
- Muscle, Smooth / metabolism
- Myosin Heavy Chains / genetics
- Myosin Heavy Chains / metabolism
- Protein Isoforms / genetics
- Protein Isoforms / metabolism
- Remission Induction
- Smooth Muscle Myosins / metabolism
- Trachea / metabolism
Grant Funding
- 102751 / Canadian Institutes of Health Research
Citations
This article has been cited 10 times.- Xiong DJP, Martin JG, Lauzon AM. Airway smooth muscle function in asthma.. Front Physiol 2022;13:993406.
- Mainguy-Seers S, Boivin R, Pourali Dogaheh S, Beaudry F, Hélie P, Bonilla AG, Martin JG, Lavoie JP. Effects of azithromycin on bronchial remodeling in the natural model of severe neutrophilic asthma in horses.. Sci Rep 2022 Jan 10;12(1):446.
- Bessonnat A, Hélie P, Grimes C, Lavoie JP. Airway remodeling in horses with mild and moderate asthma.. J Vet Intern Med 2022 Jan;36(1):285-291.
- Mainguy-Seers S, Lavoie JP. Glucocorticoid treatment in horses with asthma: A narrative review.. J Vet Intern Med 2021 Jul;35(4):2045-2057.
- Anthracopoulos MB, Everard ML. Asthma: A Loss of Post-natal Homeostatic Control of Airways Smooth Muscle With Regression Toward a Pre-natal State.. Front Pediatr 2020;8:95.
- Raudsepp T, Finno CJ, Bellone RR, Petersen JL. Ten years of the horse reference genome: insights into equine biology, domestication and population dynamics in the post-genome era.. Anim Genet 2019 Dec;50(6):569-597.
- Issouf M, Vargas A, Boivin R, Lavoie JP. SRSF6 is upregulated in asthmatic horses and involved in the MYH11 SMB expression.. Physiol Rep 2018 Oct;6(20):e13896.
- Kuo CY, Huang WC, Liou CJ, Chen LC, Shen JJ, Kuo ML. Tomatidine Attenuates Airway Hyperresponsiveness and Inflammation by Suppressing Th2 Cytokines in a Mouse Model of Asthma.. Mediators Inflamm 2017;2017:5261803.
- Murcia RY, Vargas A, Lavoie JP. The Interleukin-17 Induced Activation and Increased Survival of Equine Neutrophils Is Insensitive to Glucocorticoids.. PLoS One 2016;11(5):e0154755.
- Matusovsky OS, Kachmar L, Ijpma G, Bates G, Zitouni N, Benedetti A, Lavoie JP, Lauzon AM. Peripheral Airway Smooth Muscle, but Not the Trachealis, Is Hypercontractile in an Equine Model of Asthma.. Am J Respir Cell Mol Biol 2016 May;54(5):718-27.
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