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The cardiac protein αT-catenin contributes to chemical-induced asthma.

Abstract
Ten to 25% of adult asthma is occupational induced, a subtype caused by exposure to workplace chemicals. A recent genomewide association study identified single-nucleotide polymorphisms in the cardiac protein αT-catenin (αT-cat) that correlated with the incidence and severity of toluene diisocyanate (TDI) occupational asthma. αT-cat is a critical mediator of cell-cell adhesion and is predominantly expressed in cardiomyocytes, but its connection to asthma remains unknown. Therefore, we sought to determine the primary αT-cat-expressing cell type in the lung and its contribution to lung physiology in a murine model of TDI asthma. We show that αT-cat is expressed in lung within the cardiac sheath of pulmonary veins. Mechanically ventilated αT-cat knockout (KO) mice exhibit a significantly increased pressure-volume curve area compared with wild-type (WT) mice, suggesting that αT-cat loss affects lung hysteresis. Using a murine model of TDI asthma, we find that αT-cat KO mice show increased airway hyperresponsiveness to methacholine compared with WT mice. Bronchoalveolar lavage reveals only a mild macrophage-dominant inflammation that is not significantly different between WT and KO mice. These data suggest that αT-cat may contribute to asthma through a mechanism independent of inflammation and related to heart and pulmonary vein dysfunction.
AuthorsStephen Sai Folmsbee, Luisa Morales-Nebreda, Jolanda Van Hengel, Koen Tyberghein, Frans Van Roy, G R Scott Budinger, Paul J Bryce, Cara J Gottardi
JournalAmerican journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 308 Issue 3 Pg. L253-8 (Feb 01 2015) ISSN: 1522-1504 [Electronic] United States
PMID25480337 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 the American Physiological Society.
Chemical References
  • Air Pollutants
  • CTNNA3 protein, mouse
  • alpha Catenin
  • Toluene 2,4-Diisocyanate
Topics
  • Air Pollutants (toxicity)
  • Animals
  • Asthma, Occupational (chemically induced, metabolism)
  • Cells, Cultured
  • Female
  • Humans
  • Intercellular Junctions (metabolism)
  • Lung (blood supply, metabolism, pathology)
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocytes, Cardiac (metabolism)
  • Pulmonary Veins (metabolism, pathology)
  • Toluene 2,4-Diisocyanate (toxicity)
  • alpha Catenin (metabolism)

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