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Protease-activated receptor 2 mediates mucus secretion in the airway submucosal gland

Hyun Jae Lee1, Yu-Mi Yang, Kyubo Kim

  • 1Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.

Plos One
|August 24, 2012
PubMed

Insights

Protease-activated receptor 2 (PAR2) activation triggers mucus secretion in human airways. This calcium-dependent process in airway glands is independent of cystic fibrosis transmembrane conductance regulator function.

Area of Science:

  • Respiratory Medicine
  • Cellular Biology
  • Gastroenterology

Background:

  • Protease-activated receptor 2 (PAR2) is a G protein-coupled receptor found in airway epithelia and smooth muscle.
  • PAR2 is implicated in the pathogenesis of airway inflammation.

Purpose of the Study:

  • To investigate the role of PAR2 in inducing mucus secretion from human airway glands.
  • To elucidate the underlying molecular mechanisms of PAR2-mediated mucus secretion.

Main Methods:

  • Dissection of human, porcine, and murine airway tissues containing submucosal glands.
  • Visualization and quantification of glandular secretions using optical monitoring in a physiological chamber.
  • Measurement of intracellular calcium ([Ca(2+)](i)) using Fura2-AM and spectrofluorometry.
  • Assessment of PAR2-AP effects in wild-type and cystic fibrosis transmembrane conductance regulator (CFTR) mutant mice, including PAR-2 knockouts.

Main Results:

  • PAR2 activation by PAR2-activating peptide (PAR2-AP) stimulated mucus secretion in human airway glands, increasing intracellular calcium.
  • The PAR2-AP-induced secretion in human airways reached approximately 30% of the carbachol response.
  • Porcine airway glands showed heightened sensitivity to PAR2-AP, with responses dependent on calcium and anion secretion.
  • PAR2-AP induced significant mucus secretion in both wild-type and ΔF508 CFTR mutant mice, but not in PAR-2 knockout mice.

Conclusions:

  • PAR2-AP acts as a potent agonist for mucus secretion from airway glands.
  • The mechanism of PAR2-mediated mucus secretion is calcium-dependent.
  • This secretory pathway is independent of cystic fibrosis transmembrane conductance regulator (CFTR) function.

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