دورية أكاديمية
Intrapulmonary airway smooth muscle is hyperreactive with a distinct proteome in asthma.
| العنوان: | Intrapulmonary airway smooth muscle is hyperreactive with a distinct proteome in asthma. |
|---|---|
| المؤلفون: | Ijpma G; Dept of Medicine, McGill University, Montreal, QC, Canada.; Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, QC, Canada., Kachmar L; Dept of Medicine, McGill University, Montreal, QC, Canada.; Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, QC, Canada., Panariti A; Dept of Medicine, McGill University, Montreal, QC, Canada.; Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, QC, Canada., Matusovsky OS; Dept of Kinesiology and Physical Education, McGill University, Montreal, QC, Canada., Torgerson D; Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.; McGill University and Génome Québec Innovation Centre, Montreal, QC, Canada., Benedetti A; Dept of Medicine, McGill University, Montreal, QC, Canada.; Dept of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada.; Respiratory Epidemiology and Clinical Research Unit, McGill University Health Centre, Montreal, QC, Canada., Lauzon AM; Dept of Medicine, McGill University, Montreal, QC, Canada anne-marie.lauzon@mcgill.ca.; Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, QC, Canada. |
| المصدر: | The European respiratory journal [Eur Respir J] 2020 Jul 02; Vol. 56 (1). Date of Electronic Publication: 2020 Jul 02 (Print Publication: 2020). |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: European Respiratory Society Country of Publication: England NLM ID: 8803460 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1399-3003 (Electronic) Linking ISSN: 09031936 NLM ISO Abbreviation: Eur Respir J Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Sheffield, United Kingdom : European Respiratory Society Original Publication: Copenhagen : Published jointly by the Society and Munksgaard, 1988- |
| مواضيع طبية MeSH: | Asthma* , Proteome*, Bronchi ; Humans ; Muscle Contraction ; Muscle, Smooth ; Proteomics |
| مستخلص: | Constriction of airways during asthmatic exacerbation is the result of airway smooth muscle (ASM) contraction. Although it is generally accepted that ASM is hypercontractile in asthma, this has not been unambiguously demonstrated. Whether airway hyperresponsiveness (AHR) is the result of increased ASM mass alone or also increased contractile force generation per unit of muscle directly determines the potential avenues for treatment.To assess whether ASM is hypercontractile we performed a series of mechanics measurements on isolated ASM from intrapulmonary airways and trachealis from human lungs. We analysed the ASM and whole airway proteomes to verify if proteomic shifts contribute to changes in ASM properties.We report an increase in isolated ASM contractile stress and stiffness specific to asthmatic human intrapulmonary bronchi, the site of increased airway resistance in asthma. Other contractile parameters were not altered. Principal component analysis (PCA) of unbiased mass spectrometry data showed clear clustering of asthmatic subjects with respect to ASM specific proteins. The whole airway proteome showed upregulation of structural proteins. We did not find any evidence for a difference in the regulation of myosin activity in the asthmatic ASM.In conclusion, we showed that ASM is indeed hyperreactive at the level of intrapulmonary airways in asthma. We identified several proteins that are upregulated in asthma that could contribute to hyperreactivity. Our data also suggest enhanced force transmission associated with enrichment of structural proteins in the whole airway. These findings may lead to novel directions for treatment development in asthma. Competing Interests: Conflict of interest: G. Ijpma has nothing to disclose. Conflict of interest: L. Kachmar has nothing to disclose. Conflict of interest: A. Panariti has nothing to disclose. Conflict of interest: O.S. Matusovsky has nothing to disclose. Conflict of interest: D. Torgerson has nothing to disclose. Conflict of interest: A. Benedetti has nothing to disclose. Conflict of interest: A-M. Lauzon has nothing to disclose. (Copyright ©ERS 2020.) |
| معلومات مُعتمدة: | R01 HL103405 United States HL NHLBI NIH HHS; International Canadian Institute for Health Research |
| المشرفين على المادة: | 0 (Proteome) |
| تواريخ الأحداث: | Date Created: 20200418 Date Completed: 20210621 Latest Revision: 20210621 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1183/13993003.02178-2019 |
| PMID: | 32299863 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1399-3003 |
|---|---|
| DOI: | 10.1183/13993003.02178-2019 |