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

Stephen Sai Folmsbee, Luisa Morales-Nebreda, Jolanda Van Henge, Koen Tyberghein, Frans Van Roy, G. R.Scott Budinger, Paul J. Bryce, Cara J. Gottardi*

*Corresponding author for this work

Research output: Contribution to journalArticle

10 Scopus citations

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 pressurevolume 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.

Original languageEnglish (US)
Pages (from-to)L253-L258
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume308
Issue number3
DOIs
StatePublished - 2015

Keywords

  • Cell-cell adhesion
  • Lung hysteresis
  • Occupational asthma
  • αT-catenin

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Fingerprint Dive into the research topics of 'The cardiac protein αT-catenin contributes to chemical-induced asthma'. Together they form a unique fingerprint.

  • Cite this