SFPQ rescues F508del-CFTR expression and function in cystic fibrosis bronchial epithelial cells

Abstract Cystic fibrosis (CF) occurs as a result of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which lead to misfolding, trafficking defects, and impaired function of the CFTR protein. Splicing factor proline/glutamine-rich (SFPQ) is a multifunctional nuclear R...

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Autores principales:	Parameet Kumar, Dharmendra Kumar Soni, Chaitali Sen, Mads B. Larsen, Krystyna Mazan-Mamczarz, Yulan Piao, Supriyo De, Myriam Gorospe, Raymond A. Frizzell, Roopa Biswas
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8c85c837ff6341c9a9a4cf53d4a47860
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spelling	oai:doaj.org-article:8c85c837ff6341c9a9a4cf53d4a478602021-12-02T15:10:33ZSFPQ rescues F508del-CFTR expression and function in cystic fibrosis bronchial epithelial cells10.1038/s41598-021-96141-w2045-2322https://doaj.org/article/8c85c837ff6341c9a9a4cf53d4a478602021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96141-whttps://doaj.org/toc/2045-2322Abstract Cystic fibrosis (CF) occurs as a result of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which lead to misfolding, trafficking defects, and impaired function of the CFTR protein. Splicing factor proline/glutamine-rich (SFPQ) is a multifunctional nuclear RNA-binding protein (RBP) implicated in the regulation of gene expression pathways and intracellular trafficking. Here, we investigated the role of SFPQ in the regulation of the expression and function of F508del-CFTR in CF lung epithelial cells. We find that the expression of SFPQ is reduced in F508del-CFTR CF epithelial cells compared to WT-CFTR control cells. Interestingly, the overexpression of SFPQ in CF cells increases the expression as well as rescues the function of F508del-CFTR. Further, comprehensive transcriptome analyses indicate that SFPQ plays a key role in activating the mutant F508del-CFTR by modulating several cellular signaling pathways. This is the first report on the role of SFPQ in the regulation of expression and function of F508del-CFTR in CF lung disease. Our findings provide new insights into SFPQ-mediated molecular mechanisms and point to possible novel epigenetic therapeutic targets for CF and related pulmonary diseases.Parameet KumarDharmendra Kumar SoniChaitali SenMads B. LarsenKrystyna Mazan-MamczarzYulan PiaoSupriyo DeMyriam GorospeRaymond A. FrizzellRoopa BiswasNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Parameet Kumar Dharmendra Kumar Soni Chaitali Sen Mads B. Larsen Krystyna Mazan-Mamczarz Yulan Piao Supriyo De Myriam Gorospe Raymond A. Frizzell Roopa Biswas SFPQ rescues F508del-CFTR expression and function in cystic fibrosis bronchial epithelial cells
description	Abstract Cystic fibrosis (CF) occurs as a result of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which lead to misfolding, trafficking defects, and impaired function of the CFTR protein. Splicing factor proline/glutamine-rich (SFPQ) is a multifunctional nuclear RNA-binding protein (RBP) implicated in the regulation of gene expression pathways and intracellular trafficking. Here, we investigated the role of SFPQ in the regulation of the expression and function of F508del-CFTR in CF lung epithelial cells. We find that the expression of SFPQ is reduced in F508del-CFTR CF epithelial cells compared to WT-CFTR control cells. Interestingly, the overexpression of SFPQ in CF cells increases the expression as well as rescues the function of F508del-CFTR. Further, comprehensive transcriptome analyses indicate that SFPQ plays a key role in activating the mutant F508del-CFTR by modulating several cellular signaling pathways. This is the first report on the role of SFPQ in the regulation of expression and function of F508del-CFTR in CF lung disease. Our findings provide new insights into SFPQ-mediated molecular mechanisms and point to possible novel epigenetic therapeutic targets for CF and related pulmonary diseases.
format	article
author	Parameet Kumar Dharmendra Kumar Soni Chaitali Sen Mads B. Larsen Krystyna Mazan-Mamczarz Yulan Piao Supriyo De Myriam Gorospe Raymond A. Frizzell Roopa Biswas
author_facet	Parameet Kumar Dharmendra Kumar Soni Chaitali Sen Mads B. Larsen Krystyna Mazan-Mamczarz Yulan Piao Supriyo De Myriam Gorospe Raymond A. Frizzell Roopa Biswas
author_sort	Parameet Kumar
title	SFPQ rescues F508del-CFTR expression and function in cystic fibrosis bronchial epithelial cells
title_short	SFPQ rescues F508del-CFTR expression and function in cystic fibrosis bronchial epithelial cells
title_full	SFPQ rescues F508del-CFTR expression and function in cystic fibrosis bronchial epithelial cells
title_fullStr	SFPQ rescues F508del-CFTR expression and function in cystic fibrosis bronchial epithelial cells
title_full_unstemmed	SFPQ rescues F508del-CFTR expression and function in cystic fibrosis bronchial epithelial cells
title_sort	sfpq rescues f508del-cftr expression and function in cystic fibrosis bronchial epithelial cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8c85c837ff6341c9a9a4cf53d4a47860
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SFPQ rescues F508del-CFTR expression and function in cystic fibrosis bronchial epithelial cells

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