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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Formato: | Artículo |
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Elsevier
2019
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Acceso en línea: | https://repositorio.uca.edu.ar/handle/123456789/8618 |
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I33-R139123456789-8618 |
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Universidad Católica Argentina |
institution_str |
I-33 |
repository_str |
R-139 |
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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 |
bdutipo_str |
Repositorios |
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