Essential role of Smad3 in the inhibition of inflammation-induced PPARbeta/delta expression.

Détails

ID Serval
serval:BIB_C76B9D75FB34
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Essential role of Smad3 in the inhibition of inflammation-induced PPARbeta/delta expression.
Périodique
EMBO Journal
Auteur(s)
Tan N.S., Michalik L., Di-Poï N., Ng C.Y., Mermod N., Roberts A.B., Desvergne B., Wahli W.
ISSN
0261-4189
Statut éditorial
Publié
Date de publication
2004
Peer-reviewed
Oui
Volume
23
Numéro
21
Pages
4211-4221
Langue
anglais
Résumé
Wound healing proceeds by the concerted action of a variety of signals that have been well identified. However, the mechanisms integrating them and coordinating their effects are poorly known. Herein, we reveal how PPARbeta/delta (PPAR: peroxisome proliferator-activated receptor) follows a balanced pattern of expression controlled by a crosstalk between inflammatory cytokines and TGF-beta1. Whereas conditions that mimic the initial inflammatory events stimulate PPARbeta/delta expression, TGF-beta1/Smad3 suppresses this inflammation-induced PPARbeta/delta transcription, as seen in the late re-epithelialization/remodeling events. This TGF-beta1/Smad3 action involves an inhibitory effect on AP-1 activity and DNA binding that results in an inhibition of the AP-1-driven induction of the PPARbeta/delta promoter. As expected from these observations, wound biopsies from Smad3-null mice showed sustained PPARbeta expression as compared to those of their wild-type littermates. Together, these findings suggest a mechanism for setting the necessary balance between inflammatory signals, which trigger PPARbeta/delta expression, and TGF-beta1/Smad3 that governs the timely decrease of this expression as wound healing proceeds to completion.
Mots-clé
Animals, Cell Line, Cytokines, DNA-Binding Proteins, Gene Expression Regulation, Genes, Reporter, Inflammation, Mice, Mice, Knockout, Nuclear Proteins, PPAR delta, PPAR-beta, Promoter Regions, Genetic, Protein Binding, Proto-Oncogene Proteins c-jun, Signal Transduction, Smad3 Protein, Trans-Activators, Transforming Growth Factor beta, Transforming Growth Factor beta1, Wound Healing
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 10:41
Dernière modification de la notice
20/08/2019 15:42
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