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The cardiomyocyte protein ?T-catenin contributes to asthma through regulating pulmonary vein inflammation.

ABSTRACT: BACKGROUND:Recent genome-wide association studies have identified single nucleotide polymorphisms in the gene encoding the protein ?T-catenin (CTNNA3) that correlate with both steroid-resistant atopic asthma and asthmatic exacerbations. ?-Catenins are important mediators of cell-cell adhesion, and ?T-catenin is predominantly expressed in cardiomyocytes. In the lung ?T-catenin appears to be exclusively expressed in cardiomyocytes surrounding the pulmonary veins (PVs), but its contribution to atopic asthma remains unknown. OBJECTIVE:We sought to understand the role of ?T-catenin in asthma pathogenesis. METHODS:We used ?T-catenin knockout mice and a house dust mite (HDM) extract model of atopic asthma, with assessment by means of forced oscillation, bronchoalveolar lavage, and histologic analysis. RESULTS:We found that the genetic loss of ?T-catenin in mice largely attenuated HDM-induced airway inflammation and airway hyperresponsiveness to methacholine. Mice lacking ?T-catenin that were exposed to HDM extract had reduced PV inflammation, specifically near the large veins surrounded by cardiac cells. The proximity of the airways to PVs correlated with the severity of airway goblet cell metaplasia, suggesting that PVs can influence the inflammatory milieu of adjacent airways. Loss of ?T-catenin led to compensatory upregulation of ?E-catenin, which itself has a defined anti-inflammatory function. CONCLUSION:These data mechanistically support previous clinical and genetic associations between ?T-catenin and the development of atopic asthma and suggest that PVs might have an underappreciated role in allergic airway inflammation.

SUBMITTER: Folmsbee SS

PROVIDER: S-EPMC4931945 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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The cardiomyocyte protein αT-catenin contributes to asthma through regulating pulmonary vein inflammation.

Folmsbee Stephen Sai SS Budinger G R Scott GRS Bryce Paul J PJ Gottardi Cara J CJ

The Journal of allergy and clinical immunology 20160303 1

<h4>Background</h4>Recent genome-wide association studies have identified single nucleotide polymorphisms in the gene encoding the protein αT-catenin (CTNNA3) that correlate with both steroid-resistant atopic asthma and asthmatic exacerbations. α-Catenins are important mediators of cell-cell adhesion, and αT-catenin is predominantly expressed in cardiomyocytes. In the lung αT-catenin appears to be exclusively expressed in cardiomyocytes surrounding the pulmonary veins (PVs), but its contribution ...[more]

PMID: 26947180

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The cardiomyocyte protein ?T-catenin contributes to asthma through regulating pulmonary vein inflammation.

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The cardiomyocyte protein αT-catenin contributes to asthma through regulating pulmonary vein inflammation.

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