Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR function

Autores
Massip Copiz, María Macarena; Clauzure, Mariángeles; Valdivieso, Ángel Gabriel; Santa Coloma, Tomás Antonio
Año de publicación
2018
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: CFTR is a cAMP-regulated chloride channel, whose mutations produce cystic fibrosis. The impairment of CFTR activity increases the intracellular Cl- concentration, which in turn produces an increased interleukin-1β (IL-1β) secretion. The secreted IL-1β then induces an autocrine positive feedback loop, further stimulating IL-1β priming and secretion. Since IL-1β can transactivate the epidermal growth factor receptor (EGFR), we study here the levels of expression for different EGFR ligands in Caco-2/pRS26 cells (expressing shRNA against CFTR resulting in a reduced CFTR expression and activity). The epiregulin (EREG), amphiregulin (AREG), and heparin binding EGF like growth factor (HBEGF) mRNAs, were found overexpressed in Caco-2/pRS26 cells. The EREG mRNA had the highest differential expression and was further characterized. In agreement with its mRNA levels, Western blots (WB) showed increased EREG levels in CFTR-impaired cells. In addition, EREG mRNA and protein levels were stimulated by incubation with exogenous IL-1β and inhibited by the Interleukin 1 receptor type I (IL1R1) antagonist IL1RN, suggesting that the overexpression of EREG is a consequence of the autocrine IL-1β loop previously described for these cells. In addition, the JNK inhibitor SP600125, and the EGFR inhibitors AG1478 and PD168393, also had an inhibitory effect on EREG expression, suggesting that EGFR, activated in Caco-2/pRS26 cells, is involved in the observed EREG upregulation. In conclusion, in Caco-2 CFTR-shRNA cells, the EGFR ligand EREG is overexpressed due to an active IL-1β autocrine loop that indirectly activates EGFR, constituting new signaling effectors for the CFTR signaling pathway, downstream of CFTR, Cl- , and IL-1β.
Agencia Nacional de Promoción Científica y Tecnológica
Consejo Nacional de Investigaciones Científicas y Técnicas
Pontificia Universidad Católica Argentina
Fuente
Journal of Cellular Biochemistry. 2018;119(3):2911-2922
Materia
PROTEINAS
FIBROSIS QUISTICA
GENES CFTR DEPENDIENTES
CELULAS EPITELIALES
FISIOLOGIA
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:123456789/8915
Acceder
id RIUCA_2f24f2ee57bd07c78e6ad0ccd023dff2
oai_identifier_str oai:ucacris:123456789/8915
network_acronym_str RIUCA
repository_id_str 2585
network_name_str Repositorio Institucional (UCA)
spelling Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR functionMassip Copiz, María MacarenaClauzure, MariángelesValdivieso, Ángel GabrielSanta Coloma, Tomás AntonioPROTEINASFIBROSIS QUISTICAGENES CFTR DEPENDIENTESCELULAS EPITELIALESFISIOLOGIAFil: 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: CFTR is a cAMP-regulated chloride channel, whose mutations produce cystic fibrosis. The impairment of CFTR activity increases the intracellular Cl- concentration, which in turn produces an increased interleukin-1β (IL-1β) secretion. The secreted IL-1β then induces an autocrine positive feedback loop, further stimulating IL-1β priming and secretion. Since IL-1β can transactivate the epidermal growth factor receptor (EGFR), we study here the levels of expression for different EGFR ligands in Caco-2/pRS26 cells (expressing shRNA against CFTR resulting in a reduced CFTR expression and activity). The epiregulin (EREG), amphiregulin (AREG), and heparin binding EGF like growth factor (HBEGF) mRNAs, were found overexpressed in Caco-2/pRS26 cells. The EREG mRNA had the highest differential expression and was further characterized. In agreement with its mRNA levels, Western blots (WB) showed increased EREG levels in CFTR-impaired cells. In addition, EREG mRNA and protein levels were stimulated by incubation with exogenous IL-1β and inhibited by the Interleukin 1 receptor type I (IL1R1) antagonist IL1RN, suggesting that the overexpression of EREG is a consequence of the autocrine IL-1β loop previously described for these cells. In addition, the JNK inhibitor SP600125, and the EGFR inhibitors AG1478 and PD168393, also had an inhibitory effect on EREG expression, suggesting that EGFR, activated in Caco-2/pRS26 cells, is involved in the observed EREG upregulation. In conclusion, in Caco-2 CFTR-shRNA cells, the EGFR ligand EREG is overexpressed due to an active IL-1β autocrine loop that indirectly activates EGFR, constituting new signaling effectors for the CFTR signaling pathway, downstream of CFTR, Cl- , and IL-1β.Agencia Nacional de Promoción Científica y TecnológicaConsejo Nacional de Investigaciones Científicas y TécnicasPontificia Universidad Católica ArgentinaWiley2018info: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/123456789/89150730-2312 (impreso)1097-4644 (online)10.1002/jcb.2648329091309Massip‐Copiz M, Clauzure M, Valdivieso ÁG, Santa‐Coloma TA. Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR function [en línea]. Journal of Cellular Biochemistry. 2018;119(3):2911-2922. doi:10.1002/jcb.26483 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/8915Journal of Cellular Biochemistry. 2018;119(3):2911-2922reponame:Repositorio Institucional (UCA)instname:Pontificia Universidad Católica Argentinaenginfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/4.0/2025-07-03T10:56:58Zoai:ucacris:123456789/8915instacron:UCAInstitucionalhttps://repositorio.uca.edu.ar/Universidad privadaNo correspondehttps://repositorio.uca.edu.ar/oaiclaudia_fernandez@uca.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:25852025-07-03 10:56:58.906Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentinafalse
dc.title.none.fl_str_mv Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR function
title Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR function
spellingShingle Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR function
Massip Copiz, María Macarena
PROTEINAS
FIBROSIS QUISTICA
GENES CFTR DEPENDIENTES
CELULAS EPITELIALES
FISIOLOGIA
title_short Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR function
title_full Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR function
title_fullStr Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR function
title_full_unstemmed Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR function
title_sort Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR function
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 PROTEINAS
FIBROSIS QUISTICA
GENES CFTR DEPENDIENTES
CELULAS EPITELIALES
FISIOLOGIA
topic PROTEINAS
FIBROSIS QUISTICA
GENES CFTR DEPENDIENTES
CELULAS EPITELIALES
FISIOLOGIA
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: CFTR is a cAMP-regulated chloride channel, whose mutations produce cystic fibrosis. The impairment of CFTR activity increases the intracellular Cl- concentration, which in turn produces an increased interleukin-1β (IL-1β) secretion. The secreted IL-1β then induces an autocrine positive feedback loop, further stimulating IL-1β priming and secretion. Since IL-1β can transactivate the epidermal growth factor receptor (EGFR), we study here the levels of expression for different EGFR ligands in Caco-2/pRS26 cells (expressing shRNA against CFTR resulting in a reduced CFTR expression and activity). The epiregulin (EREG), amphiregulin (AREG), and heparin binding EGF like growth factor (HBEGF) mRNAs, were found overexpressed in Caco-2/pRS26 cells. The EREG mRNA had the highest differential expression and was further characterized. In agreement with its mRNA levels, Western blots (WB) showed increased EREG levels in CFTR-impaired cells. In addition, EREG mRNA and protein levels were stimulated by incubation with exogenous IL-1β and inhibited by the Interleukin 1 receptor type I (IL1R1) antagonist IL1RN, suggesting that the overexpression of EREG is a consequence of the autocrine IL-1β loop previously described for these cells. In addition, the JNK inhibitor SP600125, and the EGFR inhibitors AG1478 and PD168393, also had an inhibitory effect on EREG expression, suggesting that EGFR, activated in Caco-2/pRS26 cells, is involved in the observed EREG upregulation. In conclusion, in Caco-2 CFTR-shRNA cells, the EGFR ligand EREG is overexpressed due to an active IL-1β autocrine loop that indirectly activates EGFR, constituting new signaling effectors for the CFTR signaling pathway, downstream of CFTR, Cl- , and IL-1β.
Agencia Nacional de Promoción Científica y Tecnológica
Consejo Nacional de Investigaciones Científicas y Técnicas
Pontificia Universidad Católica Argentina
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 2018
dc.date.none.fl_str_mv 2018
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/123456789/8915
0730-2312 (impreso)
1097-4644 (online)
10.1002/jcb.26483
29091309
Massip‐Copiz M, Clauzure M, Valdivieso ÁG, Santa‐Coloma TA. Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR function [en línea]. Journal of Cellular Biochemistry. 2018;119(3):2911-2922. doi:10.1002/jcb.26483 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/8915
url https://repositorio.uca.edu.ar/handle/123456789/8915
identifier_str_mv 0730-2312 (impreso)
1097-4644 (online)
10.1002/jcb.26483
29091309
Massip‐Copiz M, Clauzure M, Valdivieso ÁG, Santa‐Coloma TA. Epiregulin (EREG) is upregulated through an IL-1β autocrine loop in Caco-2 epithelial cells with reduced CFTR function [en línea]. Journal of Cellular Biochemistry. 2018;119(3):2911-2922. doi:10.1002/jcb.26483 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/8915
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 Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv Journal of Cellular Biochemistry. 2018;119(3):2911-2922
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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