HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 284, Issue 2, 1234-1241, January 9, 2009

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 284/2/1234    most recent M806548200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kress, E. Articles by Plateroti, M. Search for Related Content PubMed PubMed Citation Articles by Kress, E. Articles by Plateroti, M. Social Bookmarking                      What's this?

The Frizzled-related sFRP2 Gene Is a Target of Thyroid Hormone Receptor 1 and Activates β-Catenin Signaling in Mouse Intestine^*

From the Université de Lyon, Université Claude Bernard Lyon 1, Ecole Normale Supérieure de Lyon, INRA, CNRS, Institut de Génomique Fonctionnelle de Lyon, 69364 Lyon, France

The thyroid hormone receptor TR1 regulates intestinal development and homeostasis by controlling epithelial proliferation in the crypts. This involves positive control of the Wnt/β-catenin pathway. To further investigate the effect of thyroid hormone-TR1 signaling on the intestinal epithelium proliferating compartment, we performed a comparative transcription profile analysis on laser microdissected crypt cells recovered from wild type animals with normal or perturbed hormonal status, as well as from TR knock-out mice. Statistical analysis and an in silico approach allowed us to identify 179 differentially regulated genes and to group them into organized functional networks. We focused on the "cell cycle/cell proliferation" network and, in particular, on the Frizzled-related protein sFRP2, whose expression was greatly increased in response to thyroid hormones. In vitro and in vivo analyses showed that the expression of sFRP2 is directly regulated by TR1 and that it activates β-catenin signaling via Frizzled receptors. Indeed, sFRP2 stabilizes β-catenin, activates its target genes, and enhances cell proliferation. In conclusion, these new data, in conjunction with our previous results, indicate a complex interplay between TR1 and components of the Wnt/β-catenin pathway. Moreover, we describe in this study a novel mechanism of action of sFRP2, responsible for the activation of β-catenin signaling.

Received for publication, August 22, 2008 , and in revised form, November 6, 2008.

^* This work was supported in part by the Reseau National des Genopoles Project 186, Agence Nationale pour la Recherche Grant ANR-06-BLAN-0232-01, Program Equipe Labelisée of the Ligue Nationale Contre le Cancer, and the European Network of excellence CRESCENDO. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Materials and Methods, Figs. S1-S8, and Table S1.

¹ Studentship supported by the Ligue Nationale Contre le Cancer.

² To whom correspondence should be addressed: Institut de Génomique Fonctionnelle de Lyon, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France. Tel.: 33-472728536; Fax: 33-472728080; E-mail: Michela.Plateroti{at}ens-lyon.fr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?