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

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 expr...

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Autores principales: Massip Copiz, María Macarena, Clauzure, Mariángeles, Valdivieso, Ángel Gabriel, Santa Coloma, Tomás Antonio
Formato: Artículo
Lenguaje:Inglés
Publicado: Elsevier 2019
Materias:
FIBROSIS QUISTICA
MITOCONDRIAS
GENES
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/8618
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-8618
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic FIBROSIS QUISTICA
MITOCONDRIAS
GENES
spellingShingle FIBROSIS QUISTICA
MITOCONDRIAS
GENES
Massip Copiz, María Macarena
Clauzure, Mariángeles
Valdivieso, Ángel Gabriel
Santa Coloma, Tomás Antonio
CFTR impairment upregulates c-Src activity through IL-1β autocrine signaling
topic_facet FIBROSIS QUISTICA
MITOCONDRIAS
GENES
description 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.
format Artículo
author Massip Copiz, María Macarena
Clauzure, Mariángeles
Valdivieso, Ángel Gabriel
Santa Coloma, Tomás Antonio
author_facet Massip Copiz, María Macarena
Clauzure, Mariángeles
Valdivieso, Ángel Gabriel
Santa Coloma, Tomás Antonio
author_sort Massip Copiz, María Macarena
title CFTR impairment upregulates c-Src activity through IL-1β autocrine signaling
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
publisher Elsevier
publishDate 2019
url https://repositorio.uca.edu.ar/handle/123456789/8618
work_keys_str_mv AT massipcopizmariamacarena cftrimpairmentupregulatescsrcactivitythroughil1bautocrinesignaling
AT clauzuremariangeles cftrimpairmentupregulatescsrcactivitythroughil1bautocrinesignaling
AT valdiviesoangelgabriel cftrimpairmentupregulatescsrcactivitythroughil1bautocrinesignaling
AT santacolomatomasantonio cftrimpairmentupregulatescsrcactivitythroughil1bautocrinesignaling
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