Key Role for Store-Operated Ca2+ Channels in Activating Gene Expression in Human Airway Bronchial Epithelial Cells

Ca2+ entry into airway epithelia is important for activation of the NFAT family of transcription factors and expression of genes including epidermal growth factor that help orchestrate local inflammatory responses. However, the identity of epithelial Ca2+ channel that activates these transcriptional...

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Main Authors:	Samanta, Krishna, Bakowski, Daniel, Parekh, Anant B.
Format:	Online
Language:	English
Published:	Public Library of Science 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144895/

id	pubmed-4144895
recordtype	oai_dc
spelling	pubmed-41448952014-08-29 Key Role for Store-Operated Ca2+ Channels in Activating Gene Expression in Human Airway Bronchial Epithelial Cells Samanta, Krishna Bakowski, Daniel Parekh, Anant B. Research Article Ca2+ entry into airway epithelia is important for activation of the NFAT family of transcription factors and expression of genes including epidermal growth factor that help orchestrate local inflammatory responses. However, the identity of epithelial Ca2+ channel that activates these transcriptional responses is unclear. In many other non-excitable cells, store-operated Ca2+ entry is a major route for Ca2+ influx and is mediated by STIM1 and Orai1 proteins. This study was performed to determine if store-operated Ca2+ channels were expressed in human bronchial epithelial cells and, if so, whether they coupled Ca2+ entry to gene expression. Cytoplasmic Ca2+ measurements, patch clamp recordings, RNAi knockdown and functional assays were used to identify and then investigate the role of these Ca2+ channels in activating the NFAT and c-fos pathways and EGF expression. STIM1 and Orai1 mRNA transcripts as well as proteins were robustly in epithelial cells and formed functional Ca2+ channels. Ca2+ entry through the channels activated expression of c-fos and EGF as well as an NFAT-dependent reporter gene. Store-operated Ca2+ entry was also important for epithelial cell migration in a scrape wound assay. These findings indicate that store-operated Ca2+ channels play an important role in stimulating airway epithelial cell gene expression and therefore comprise a novel potential therapeutic target for the treatment of chronic asthma and related airway disorders. Public Library of Science 2014-08-26 /pmc/articles/PMC4144895/ /pubmed/25157492 http://dx.doi.org/10.1371/journal.pone.0105586 Text en © 2014 Samanta 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Samanta, Krishna Bakowski, Daniel Parekh, Anant B.
spellingShingle	Samanta, Krishna Bakowski, Daniel Parekh, Anant B. Key Role for Store-Operated Ca2+ Channels in Activating Gene Expression in Human Airway Bronchial Epithelial Cells
author_facet	Samanta, Krishna Bakowski, Daniel Parekh, Anant B.
author_sort	Samanta, Krishna
title	Key Role for Store-Operated Ca2+ Channels in Activating Gene Expression in Human Airway Bronchial Epithelial Cells
title_short	Key Role for Store-Operated Ca2+ Channels in Activating Gene Expression in Human Airway Bronchial Epithelial Cells
title_full	Key Role for Store-Operated Ca2+ Channels in Activating Gene Expression in Human Airway Bronchial Epithelial Cells
title_fullStr	Key Role for Store-Operated Ca2+ Channels in Activating Gene Expression in Human Airway Bronchial Epithelial Cells
title_full_unstemmed	Key Role for Store-Operated Ca2+ Channels in Activating Gene Expression in Human Airway Bronchial Epithelial Cells
title_sort	key role for store-operated ca2+ channels in activating gene expression in human airway bronchial epithelial cells
description	Ca2+ entry into airway epithelia is important for activation of the NFAT family of transcription factors and expression of genes including epidermal growth factor that help orchestrate local inflammatory responses. However, the identity of epithelial Ca2+ channel that activates these transcriptional responses is unclear. In many other non-excitable cells, store-operated Ca2+ entry is a major route for Ca2+ influx and is mediated by STIM1 and Orai1 proteins. This study was performed to determine if store-operated Ca2+ channels were expressed in human bronchial epithelial cells and, if so, whether they coupled Ca2+ entry to gene expression. Cytoplasmic Ca2+ measurements, patch clamp recordings, RNAi knockdown and functional assays were used to identify and then investigate the role of these Ca2+ channels in activating the NFAT and c-fos pathways and EGF expression. STIM1 and Orai1 mRNA transcripts as well as proteins were robustly in epithelial cells and formed functional Ca2+ channels. Ca2+ entry through the channels activated expression of c-fos and EGF as well as an NFAT-dependent reporter gene. Store-operated Ca2+ entry was also important for epithelial cell migration in a scrape wound assay. These findings indicate that store-operated Ca2+ channels play an important role in stimulating airway epithelial cell gene expression and therefore comprise a novel potential therapeutic target for the treatment of chronic asthma and related airway disorders.
publisher	Public Library of Science
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144895/
_version_	1613127770362085376

Key Role for Store-Operated Ca2+ Channels in Activating Gene Expression in Human Airway Bronchial Epithelial Cells

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