title: The frizzled-related sFRP2 gene is a target of thyroid hormone receptor alpha1 and activates beta-catenin signaling in mouse intestine.
abstract: The thyroid hormone receptor TRalpha1 regulates intestinal development and homeostasis by controlling epithelial proliferation in the crypts. This involves positive control of the Wnt/beta-catenin pathway. To further investigate the effect of thyroid hormone-TRalpha1 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 TRalpha1 and that it activates beta-catenin signaling via Frizzled receptors. Indeed, sFRP2 stabilizes beta-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 TRalpha1 and components of the Wnt/beta-catenin pathway. Moreover, we describe in this study a novel mechanism of action of sFRP2, responsible for the activation of beta-catenin signaling.
authors.affiliation: Université de Lyon, Université Claude Bernard Lyon 1, Ecole Normale Supérieure de Lyon, INRA, CNRS, Institut de Génomique Fonctionnelle de Lyon, 69364 Lyon, France.
authors.forename: Elsa
authors.initials: E
authors.lastname: Kress
authors.forename: Amelie
authors.initials: A
authors.lastname: Rezza
authors.forename: Julien
authors.initials: J
authors.lastname: Nadjar
authors.forename: Jacques
authors.initials: J
authors.lastname: Samarut
authors.forename: Michelina
authors.initials: M
authors.lastname: Plateroti
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D020218:Response Elements / Q000235:genetics; D015398:Signal Transduction; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D008565:Membrane Proteins; D037021:Thyroid Hormone Receptors alpha; D013963:Thyroid Hormones; D051176:beta Catenin; C491628:Sfrp2 protein, mouse; D000094742:Secreted Frizzled-Related Proteins