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

Details

Serval ID
serval:BIB_C76B9D75FB34
Type
Article: article from journal or magazin.
Collection
Publications
Title
Essential role of Smad3 in the inhibition of inflammation-induced PPARbeta/delta expression.
Journal
EMBO Journal
Author(s)
Tan N.S., Michalik L., Di-Poï N., Ng C.Y., Mermod N., Roberts A.B., Desvergne B., Wahli W.
ISSN
0261-4189
Publication state
Published
Issued date
2004
Peer-reviewed
Oui
Volume
23
Number
21
Pages
4211-4221
Language
english
Abstract
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.
Keywords
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
Yes
Create date
24/01/2008 11:41
Last modification date
20/08/2019 16:42
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