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Protease-Activated Receptor 2 Mediates Mucus Secretion in the Airway Submucosal Gland

Protease-activated receptor 2 (PAR2), a G protein-coupled receptor expressed in airway epithelia and smooth muscle, plays an important role in airway inflammation. In this study, we demonstrated that activation of PAR2 induces mucus secretion from the human airway gland and examined the underlying m...

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Autores principales: Lee, Hyun Jae, Yang, Yu-Mi, Kim, Kyubo, Shin, Dong Min, Yoon, Joo-Heon, Cho, Hyung-Ju, Choi, Jae Young
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419645/
https://www.ncbi.nlm.nih.gov/pubmed/22916223
http://dx.doi.org/10.1371/journal.pone.0043188
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author Lee, Hyun Jae
Yang, Yu-Mi
Kim, Kyubo
Shin, Dong Min
Yoon, Joo-Heon
Cho, Hyung-Ju
Choi, Jae Young
author_facet Lee, Hyun Jae
Yang, Yu-Mi
Kim, Kyubo
Shin, Dong Min
Yoon, Joo-Heon
Cho, Hyung-Ju
Choi, Jae Young
author_sort Lee, Hyun Jae
collection PubMed
description Protease-activated receptor 2 (PAR2), a G protein-coupled receptor expressed in airway epithelia and smooth muscle, plays an important role in airway inflammation. In this study, we demonstrated that activation of PAR2 induces mucus secretion from the human airway gland and examined the underlying mechanism using the porcine and murine airway glands. The mucosa with underlying submucosal glands were dissected from the cartilage of tissues, pinned with the mucosal side up at the gas/bath solution interface of a physiological chamber, and covered with oil so that secretions from individual glands could be visualized as spherical bubbles in the oil. Secretion rates were determined by optical monitoring of the bubble diameter. The Ca(2+)-sensitive dye Fura2-AM was used to determine intracellular Ca(2+) concentration ([Ca(2+)](i)) by means of spectrofluorometry. Stimulation of human tracheal mucosa with PAR2-activating peptide (PAR2-AP) elevated intracellular Ca(2+) and induced glandular secretion equal to approximately 30% of the carbachol response in the human airway. Porcine gland tissue was more sensitive to PAR2-AP, and this response was dependent on Ca(2+) and anion secretion. When the mouse trachea were exposed to PAR2-AP, large amounts of secretion were observed in both wild type and ΔF508 cystic fibrosis transmembrane conductance regulator mutant mice but there is no secretion from PAR-2 knock out mice. In conclusion, PAR2-AP is an agonist for mucus secretion from the airway gland that is Ca(2+)-dependent and cystic fibrosis transmembrane conductance regulator-independent.
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spelling pubmed-34196452012-08-22 Protease-Activated Receptor 2 Mediates Mucus Secretion in the Airway Submucosal Gland Lee, Hyun Jae Yang, Yu-Mi Kim, Kyubo Shin, Dong Min Yoon, Joo-Heon Cho, Hyung-Ju Choi, Jae Young PLoS One Research Article Protease-activated receptor 2 (PAR2), a G protein-coupled receptor expressed in airway epithelia and smooth muscle, plays an important role in airway inflammation. In this study, we demonstrated that activation of PAR2 induces mucus secretion from the human airway gland and examined the underlying mechanism using the porcine and murine airway glands. The mucosa with underlying submucosal glands were dissected from the cartilage of tissues, pinned with the mucosal side up at the gas/bath solution interface of a physiological chamber, and covered with oil so that secretions from individual glands could be visualized as spherical bubbles in the oil. Secretion rates were determined by optical monitoring of the bubble diameter. The Ca(2+)-sensitive dye Fura2-AM was used to determine intracellular Ca(2+) concentration ([Ca(2+)](i)) by means of spectrofluorometry. Stimulation of human tracheal mucosa with PAR2-activating peptide (PAR2-AP) elevated intracellular Ca(2+) and induced glandular secretion equal to approximately 30% of the carbachol response in the human airway. Porcine gland tissue was more sensitive to PAR2-AP, and this response was dependent on Ca(2+) and anion secretion. When the mouse trachea were exposed to PAR2-AP, large amounts of secretion were observed in both wild type and ΔF508 cystic fibrosis transmembrane conductance regulator mutant mice but there is no secretion from PAR-2 knock out mice. In conclusion, PAR2-AP is an agonist for mucus secretion from the airway gland that is Ca(2+)-dependent and cystic fibrosis transmembrane conductance regulator-independent. Public Library of Science 2012-08-15 /pmc/articles/PMC3419645/ /pubmed/22916223 http://dx.doi.org/10.1371/journal.pone.0043188 Text en © 2012 Lee et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lee, Hyun Jae
Yang, Yu-Mi
Kim, Kyubo
Shin, Dong Min
Yoon, Joo-Heon
Cho, Hyung-Ju
Choi, Jae Young
Protease-Activated Receptor 2 Mediates Mucus Secretion in the Airway Submucosal Gland
title Protease-Activated Receptor 2 Mediates Mucus Secretion in the Airway Submucosal Gland
title_full Protease-Activated Receptor 2 Mediates Mucus Secretion in the Airway Submucosal Gland
title_fullStr Protease-Activated Receptor 2 Mediates Mucus Secretion in the Airway Submucosal Gland
title_full_unstemmed Protease-Activated Receptor 2 Mediates Mucus Secretion in the Airway Submucosal Gland
title_short Protease-Activated Receptor 2 Mediates Mucus Secretion in the Airway Submucosal Gland
title_sort protease-activated receptor 2 mediates mucus secretion in the airway submucosal gland
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419645/
https://www.ncbi.nlm.nih.gov/pubmed/22916223
http://dx.doi.org/10.1371/journal.pone.0043188
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