TRPA1 channels: expression in non-neuronal murine lung tissues and dispensability for hyperoxia-induced alveolar epithelial hyperplasia

Pflugers Arch. 2018 Aug;470(8):1231-1241. doi: 10.1007/s00424-018-2148-6. Epub 2018 May 12.


Transient receptor potential A1 (TRPA1) channels were originally characterized in neuronal tissues but also identified in lung epithelium by staining with fluorescently coupled TRPA1 antibodies. Its exact function in non-neuronal tissues, however, is elusive. TRPA1 is activated in vitro by hypoxia and hyperoxia and is therefore a promising TRP candidate for sensing hyperoxia in pulmonary epithelial cells and for inducing alveolar epithelial hyperplasia. Here, we isolated tracheal, bronchial, and alveolar epithelial cells and show low but detectable TRPA1 mRNA levels in all these cells as well as TRPA1 protein by Western blotting in alveolar type II (AT II) cells. We quantified changes in intracellular Ca2+ ([Ca2+]i) levels induced by application of hyperoxic solutions in primary tracheal epithelial, bronchial epithelial, and AT II cells isolated from wild-type (WT) and TRPA1-deficient (TRPA1-/-) mouse lungs. In all cell types, we detected hyperoxia-induced rises in [Ca2+]i levels, which were not significantly different in TRPA1-deficient cells compared to WT cells. We also tested TRPA1 function in a mouse model for hyperoxia-induced alveolar epithelial hyperplasia. A characteristic significant increase in thickening of alveolar tissues was detected in mouse lungs after exposure to hyperoxia, but not in normoxic WT and TRPA1-/- controls. Quantification of changes in lung morphology in hyperoxic WT and TRPA1-/- mice, however, again revealed no significant changes. Therefore, TRPA1 expression does neither appear to be a key player for hyperoxia-induced changes in [Ca2+]i levels in primary lung epithelial cells, nor being essential for the development of hyperoxia-induced alveolar epithelial hyperplasia.

Keywords: Alveolar epithelial hyperplasia; Human lung tissues; Hyperoxia; Murine lung tissues; TRPA1; mRNA expression.

MeSH terms

  • Animals
  • Bronchi / metabolism
  • Cell Line
  • Epithelial Cells / metabolism*
  • Epithelium / metabolism
  • Female
  • HEK293 Cells
  • Humans
  • Hyperoxia / metabolism*
  • Hyperplasia / metabolism*
  • Lung / metabolism*
  • Male
  • Mice
  • Mice, Transgenic
  • Pulmonary Alveoli / metabolism*
  • RNA, Messenger / metabolism
  • TRPA1 Cation Channel / metabolism*


  • RNA, Messenger
  • TRPA1 Cation Channel
  • Trpa1 protein, mouse