CFTR impairment upregulates c-Src activity through IL-1β autocrine signaling

Autores
Massip Copiz, María Macarena; Clauzure, Mariángeles; Valdivieso, Ángel Gabriel; Santa Coloma, Tomás Antonio
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión aceptada
Descripción
Fil: Massip Copiz, María Macarena. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Celular y Molecular; Argentina
Fil: Massip Copiz, María Macarena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Clauzure, Mariángeles. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Celular y Molecular; Argentina
Fil: Clauzure, Mariángeles. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Valdivieso, Ángel Gabriel. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Celular y Molecular; Argentina
Fil: Valdivieso, Ángel Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Santa Coloma, Tomás Antonio. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Celular y Molecular; Argentina
Fil: Santa Coloma, Tomás Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Abstract: Cystic Fibrosis (CF) is a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Previously, we found several genes showing a differential expression in CFDE cells (epithelial cells derived from a CF patient). One corresponded to c-Src; its expression and activity was found increased in CFDE cells, acting as a signaling molecule between the CFTR activity and MUC1 overexpression. Here we report that bronchial IB3-1 cells (CF cells) also showed increased c-Src activity compared to 'CFTR-corrected' S9 cells. In addition, three different Caco-2 cell lines, each stably transfected with a different CFTR-specific shRNAs, displayed increased c-Src activity. The IL-1β receptor antagonist IL1RN reduced the c-Src activity of Caco-2/pRS26 cells (expressing a CFTR-specific shRNA). In addition, increased mitochondrial and cellular ROS levels were detected in Caco-2/pRS26 cells. ROS levels were partially reduced by incubation with PP2 (c-Src inhibitor) or IL1RN, and further reduced by using the NOX1/4 inhibitor GKT137831. Thus, IL-1β→c-Src and IL-1β→NOX signaling pathways appear to be responsible for the production of cellular and mitochondrial ROS in CFTR-KD cells. In conclusion, IL-1β constitutes a new step in the CFTR signaling pathway, located upstream of c-Src, which is stimulated in cells with impaired CFTR activity.
Fuente
Archives of Biochemistry and Biophysics. 2017;616:1-12
Materia
FIBROSIS QUISTICA
MITOCONDRIAS
GENES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
Repositorio Institucional (UCA)
Institución
Pontificia Universidad Católica Argentina
OAI Identificador
oai:ucacris:123456789/8618
Acceder
id RIUCA_0dc21ddb2688f215870c9ee023a06693
oai_identifier_str oai:ucacris:123456789/8618
network_acronym_str RIUCA
repository_id_str 2585
network_name_str Repositorio Institucional (UCA)
spelling CFTR impairment upregulates c-Src activity through IL-1β autocrine signalingMassip Copiz, María MacarenaClauzure, MariángelesValdivieso, Ángel GabrielSanta Coloma, Tomás AntonioFIBROSIS QUISTICAMITOCONDRIASGENESFil: Massip Copiz, María Macarena. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Celular y Molecular; ArgentinaFil: Massip Copiz, María Macarena. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Clauzure, Mariángeles. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Celular y Molecular; ArgentinaFil: Clauzure, Mariángeles. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Valdivieso, Ángel Gabriel. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Celular y Molecular; ArgentinaFil: Valdivieso, Ángel Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Santa Coloma, Tomás Antonio. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Celular y Molecular; ArgentinaFil: Santa Coloma, Tomás Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAbstract: Cystic Fibrosis (CF) is a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Previously, we found several genes showing a differential expression in CFDE cells (epithelial cells derived from a CF patient). One corresponded to c-Src; its expression and activity was found increased in CFDE cells, acting as a signaling molecule between the CFTR activity and MUC1 overexpression. Here we report that bronchial IB3-1 cells (CF cells) also showed increased c-Src activity compared to 'CFTR-corrected' S9 cells. In addition, three different Caco-2 cell lines, each stably transfected with a different CFTR-specific shRNAs, displayed increased c-Src activity. The IL-1β receptor antagonist IL1RN reduced the c-Src activity of Caco-2/pRS26 cells (expressing a CFTR-specific shRNA). In addition, increased mitochondrial and cellular ROS levels were detected in Caco-2/pRS26 cells. ROS levels were partially reduced by incubation with PP2 (c-Src inhibitor) or IL1RN, and further reduced by using the NOX1/4 inhibitor GKT137831. Thus, IL-1β→c-Src and IL-1β→NOX signaling pathways appear to be responsible for the production of cellular and mitochondrial ROS in CFTR-KD cells. In conclusion, IL-1β constitutes a new step in the CFTR signaling pathway, located upstream of c-Src, which is stimulated in cells with impaired CFTR activity.Elsevier2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://repositorio.uca.edu.ar/handle/123456789/86180003-986110.1016/j.abb.2017.01.00328088327Massip-Copiz MM, Clauzure M, Valdivieso ÁG, Santa-Coloma TA. CFTR impairment upregulates c-Src activity through IL-1β autocrine signaling [en línea]. Archives of Biochemistry and Biophysics. 2017;616:1-12. doi:10.1016/j.abb.2017.01.003 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/8618Archives of Biochemistry and Biophysics. 2017;616:1-12reponame:Repositorio Institucional (UCA)instname:Pontificia Universidad Católica Argentinaenginfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/4.0/2025-07-03T10:56:52Zoai:ucacris:123456789/8618instacron:UCAInstitucionalhttps://repositorio.uca.edu.ar/Universidad privadaNo correspondehttps://repositorio.uca.edu.ar/oaiclaudia_fernandez@uca.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:25852025-07-03 10:56:52.522Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentinafalse
dc.title.none.fl_str_mv CFTR impairment upregulates c-Src activity through IL-1β autocrine signaling
title CFTR impairment upregulates c-Src activity through IL-1β autocrine signaling
spellingShingle CFTR impairment upregulates c-Src activity through IL-1β autocrine signaling
Massip Copiz, María Macarena
FIBROSIS QUISTICA
MITOCONDRIAS
GENES
title_short CFTR impairment upregulates c-Src activity through IL-1β autocrine signaling
title_full CFTR impairment upregulates c-Src activity through IL-1β autocrine signaling
title_fullStr CFTR impairment upregulates c-Src activity through IL-1β autocrine signaling
title_full_unstemmed CFTR impairment upregulates c-Src activity through IL-1β autocrine signaling
title_sort CFTR impairment upregulates c-Src activity through IL-1β autocrine signaling
dc.creator.none.fl_str_mv Massip Copiz, María Macarena
Clauzure, Mariángeles
Valdivieso, Ángel Gabriel
Santa Coloma, Tomás Antonio
author Massip Copiz, María Macarena
author_facet Massip Copiz, María Macarena
Clauzure, Mariángeles
Valdivieso, Ángel Gabriel
Santa Coloma, Tomás Antonio
author_role author
author2 Clauzure, Mariángeles
Valdivieso, Ángel Gabriel
Santa Coloma, Tomás Antonio
author2_role author
author
author
dc.subject.none.fl_str_mv FIBROSIS QUISTICA
MITOCONDRIAS
GENES
topic FIBROSIS QUISTICA
MITOCONDRIAS
GENES
dc.description.none.fl_txt_mv Fil: Massip Copiz, María Macarena. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Celular y Molecular; Argentina
Fil: Massip Copiz, María Macarena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Clauzure, Mariángeles. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Celular y Molecular; Argentina
Fil: Clauzure, Mariángeles. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Valdivieso, Ángel Gabriel. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Celular y Molecular; Argentina
Fil: Valdivieso, Ángel Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Santa Coloma, Tomás Antonio. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Celular y Molecular; Argentina
Fil: Santa Coloma, Tomás Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Abstract: Cystic Fibrosis (CF) is a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Previously, we found several genes showing a differential expression in CFDE cells (epithelial cells derived from a CF patient). One corresponded to c-Src; its expression and activity was found increased in CFDE cells, acting as a signaling molecule between the CFTR activity and MUC1 overexpression. Here we report that bronchial IB3-1 cells (CF cells) also showed increased c-Src activity compared to 'CFTR-corrected' S9 cells. In addition, three different Caco-2 cell lines, each stably transfected with a different CFTR-specific shRNAs, displayed increased c-Src activity. The IL-1β receptor antagonist IL1RN reduced the c-Src activity of Caco-2/pRS26 cells (expressing a CFTR-specific shRNA). In addition, increased mitochondrial and cellular ROS levels were detected in Caco-2/pRS26 cells. ROS levels were partially reduced by incubation with PP2 (c-Src inhibitor) or IL1RN, and further reduced by using the NOX1/4 inhibitor GKT137831. Thus, IL-1β→c-Src and IL-1β→NOX signaling pathways appear to be responsible for the production of cellular and mitochondrial ROS in CFTR-KD cells. In conclusion, IL-1β constitutes a new step in the CFTR signaling pathway, located upstream of c-Src, which is stimulated in cells with impaired CFTR activity.
description Fil: Massip Copiz, María Macarena. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Celular y Molecular; Argentina
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://repositorio.uca.edu.ar/handle/123456789/8618
0003-9861
10.1016/j.abb.2017.01.003
28088327
Massip-Copiz MM, Clauzure M, Valdivieso ÁG, Santa-Coloma TA. CFTR impairment upregulates c-Src activity through IL-1β autocrine signaling [en línea]. Archives of Biochemistry and Biophysics. 2017;616:1-12. doi:10.1016/j.abb.2017.01.003 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/8618
url https://repositorio.uca.edu.ar/handle/123456789/8618
identifier_str_mv 0003-9861
10.1016/j.abb.2017.01.003
28088327
Massip-Copiz MM, Clauzure M, Valdivieso ÁG, Santa-Coloma TA. CFTR impairment upregulates c-Src activity through IL-1β autocrine signaling [en línea]. Archives of Biochemistry and Biophysics. 2017;616:1-12. doi:10.1016/j.abb.2017.01.003 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/8618
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/4.0/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Archives of Biochemistry and Biophysics. 2017;616:1-12
reponame:Repositorio Institucional (UCA)
instname:Pontificia Universidad Católica Argentina
reponame_str Repositorio Institucional (UCA)
collection Repositorio Institucional (UCA)
instname_str Pontificia Universidad Católica Argentina
repository.name.fl_str_mv Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentina
repository.mail.fl_str_mv claudia_fernandez@uca.edu.ar
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score 13.22299

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