Loss of IκB kinase β promotes myofibroblast transformation and senescence through activation of the ROS-TGFβ autocrine loop
Protein & Cell
;
(12): 338-350, 2016.
Article
Dans Anglais
| WPRIM
| ID: wpr-757141
ABSTRACT
Using forward and reverse genetics and global gene expression analyses, we explored the crosstalk between the IκB kinase β (IKKβ) and the transforming growth factor β (TGFβ) signaling pathways. We show that in vitro ablation of Ikkβ in fibroblasts led to progressive ROS accumulation and TGFβ activation, and ultimately accelerated cell migration, fibroblast-myofibroblast transformation and senescence. Mechanistically, the basal IKKβ activity was required for anti-oxidant gene expression and redox homeostasis. Lacking this activity, IKKβ-null cells showed ROS accumulation and activation of stress-sensitive transcription factor AP-1/c-Jun. AP-1/c-Jun activation led to up-regulation of the Tgfβ2 promoter, which in turn further potentiated intracellular ROS through the induction of NADPH oxidase (NOX). These data suggest that by blocking the autocrine amplification of a ROS-TGFβ loop IKKβ plays a crucial role in the prevention of fibroblast-myofibroblast transformation and senescence.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Physiologie
/
Superoxide dismutase
/
Transduction du signal
/
Régulation positive
/
Lignée cellulaire
/
Mouvement cellulaire
/
Adenoviridae
/
Facteur de croissance transformant bêta
/
Régions promotrices (génétique)
/
Vieillissement de la cellule
Limites du sujet:
Animaux
langue:
Anglais
Texte intégral:
Protein & Cell
Année:
2016
Type:
Article
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