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Functional Cooperation between KCa3.1 and TRPV4 Channels in Bronchial Smooth Muscle Cell Proliferation Associated with Chronic Asthma
Airway smooth muscle cells (SMC) proliferation contributes to the airways remodeling and irreversible airway obstruction during severe asthma, but the mechanisms of airway SMC proliferation are poorly understood. Intracellular Ca(2)(+) levels play an important role in regulating cell proliferation....
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609593/ https://www.ncbi.nlm.nih.gov/pubmed/28970794 http://dx.doi.org/10.3389/fphar.2017.00559 |
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author | Yu, Zhihua Wang, Yanxia Qin, Lu Chen, Hongzhuan |
author_facet | Yu, Zhihua Wang, Yanxia Qin, Lu Chen, Hongzhuan |
author_sort | Yu, Zhihua |
collection | PubMed |
description | Airway smooth muscle cells (SMC) proliferation contributes to the airways remodeling and irreversible airway obstruction during severe asthma, but the mechanisms of airway SMC proliferation are poorly understood. Intracellular Ca(2)(+) levels play an important role in regulating cell proliferation. We have previously reported KCa3.1 channels regulated human bronchial smooth muscle (HBSM) cells proliferation via the Ca(2+) influx as a consequence of membrane hyperpolarization. However, the role of potassium channels KCa3.1 in airway remodeling as well as the mechanism for extracellular Ca(2)(+) influx induced by the activation of KCa3.1 remains unknown. Here we demonstrated that KCa3.1 channels deficiency attenuated airway remodeling, airway inflammation, and airway hyperresponsiveness (AHR) in a mouse model of chronic asthma. The gene expressions of repressor element 1-silencing transcription factor (REST) and c-Jun, two transcriptional regulators of KCa3.1 channels, were correlated negatively or positively with KCa3.1 channels expressions both in vivo and in vitro using real-time PCR and Western blot analyses. RNAi-mediated knockdown or pharmacological blockade of KCa3.1 and TRPV4 significantly attenuated HBSM cells proliferation. Using confocal imaging and custom data analysis software, blockade of TRPV4 decreased the Ca(2)(+) influx induced by 1-EBIO-mediated KCa3.1 activation. Double-labeled staining showed that KCa3.1 and TRPV4 channels colocalized in HBSM cells. These results demonstrate that KCa3.1 channels regulate the proliferation phenotype of HBSM cells via TRPV4 channels in the process of chronic asthma, making it a potential therapeutic target to treat chronic asthma. |
format | Online Article Text |
id | pubmed-5609593 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-56095932017-10-02 Functional Cooperation between KCa3.1 and TRPV4 Channels in Bronchial Smooth Muscle Cell Proliferation Associated with Chronic Asthma Yu, Zhihua Wang, Yanxia Qin, Lu Chen, Hongzhuan Front Pharmacol Pharmacology Airway smooth muscle cells (SMC) proliferation contributes to the airways remodeling and irreversible airway obstruction during severe asthma, but the mechanisms of airway SMC proliferation are poorly understood. Intracellular Ca(2)(+) levels play an important role in regulating cell proliferation. We have previously reported KCa3.1 channels regulated human bronchial smooth muscle (HBSM) cells proliferation via the Ca(2+) influx as a consequence of membrane hyperpolarization. However, the role of potassium channels KCa3.1 in airway remodeling as well as the mechanism for extracellular Ca(2)(+) influx induced by the activation of KCa3.1 remains unknown. Here we demonstrated that KCa3.1 channels deficiency attenuated airway remodeling, airway inflammation, and airway hyperresponsiveness (AHR) in a mouse model of chronic asthma. The gene expressions of repressor element 1-silencing transcription factor (REST) and c-Jun, two transcriptional regulators of KCa3.1 channels, were correlated negatively or positively with KCa3.1 channels expressions both in vivo and in vitro using real-time PCR and Western blot analyses. RNAi-mediated knockdown or pharmacological blockade of KCa3.1 and TRPV4 significantly attenuated HBSM cells proliferation. Using confocal imaging and custom data analysis software, blockade of TRPV4 decreased the Ca(2)(+) influx induced by 1-EBIO-mediated KCa3.1 activation. Double-labeled staining showed that KCa3.1 and TRPV4 channels colocalized in HBSM cells. These results demonstrate that KCa3.1 channels regulate the proliferation phenotype of HBSM cells via TRPV4 channels in the process of chronic asthma, making it a potential therapeutic target to treat chronic asthma. Frontiers Media S.A. 2017-08-25 /pmc/articles/PMC5609593/ /pubmed/28970794 http://dx.doi.org/10.3389/fphar.2017.00559 Text en Copyright © 2017 Yu, Wang, Qin and Chen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Yu, Zhihua Wang, Yanxia Qin, Lu Chen, Hongzhuan Functional Cooperation between KCa3.1 and TRPV4 Channels in Bronchial Smooth Muscle Cell Proliferation Associated with Chronic Asthma |
title | Functional Cooperation between KCa3.1 and TRPV4 Channels in Bronchial Smooth Muscle Cell Proliferation Associated with Chronic Asthma |
title_full | Functional Cooperation between KCa3.1 and TRPV4 Channels in Bronchial Smooth Muscle Cell Proliferation Associated with Chronic Asthma |
title_fullStr | Functional Cooperation between KCa3.1 and TRPV4 Channels in Bronchial Smooth Muscle Cell Proliferation Associated with Chronic Asthma |
title_full_unstemmed | Functional Cooperation between KCa3.1 and TRPV4 Channels in Bronchial Smooth Muscle Cell Proliferation Associated with Chronic Asthma |
title_short | Functional Cooperation between KCa3.1 and TRPV4 Channels in Bronchial Smooth Muscle Cell Proliferation Associated with Chronic Asthma |
title_sort | functional cooperation between kca3.1 and trpv4 channels in bronchial smooth muscle cell proliferation associated with chronic asthma |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609593/ https://www.ncbi.nlm.nih.gov/pubmed/28970794 http://dx.doi.org/10.3389/fphar.2017.00559 |
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