The secreted Frizzled-Related Protein 2 modulates cell fate and the Wnt pathway in the murine intestinal epithelium

The secreted Frizzled-Related Proteins (sFRPs) are generally considered antagonistic to Wnt signaling. However, several studies have described their synergy and/or activation of this pathway. Our own data indicated that in the intestinal epithelium, thyroid hormone induced-expression of sFRP2 stabilizes beta-catenin, leading to induction of Wnt. The aim of this work was to investigate the role of sFRP2 in the intestinal epithelium homeostasis and its specific effect on canonical Wnt pathway. In wild type animals we observed a restricted pattern of sFRP2 protein expression at the level of the intestinal crypts. Interestingly, sFRP2(-/-) mice displayed increased apoptosis within the crypts together with a defect in cell migration. Because of altered proportion of lineage-specific committed progenitors, the sFRP2(-/-) animals also showed a decrease of absorptive differentiation counterbalanced by an increase of secretory differentiation. Regarding the action of sFRP2 on canonical Wnt pathway, the lack of sFRP2 expression in sFRP2(-/-)/TopGal animals in vivo reduced the Wnt activity. This positive action of sFRP2 on Wnt was further confirmed by in vitro studies. In conclusion, in accordance with its restricted expression profile, sFRP2 contributes to the physiology of the intestinal epithelial crypt progenitors by controlling apoptosis, cell fate decisions and the Wnt pathway. (C) 2014 Elsevier Inc. All rights reserved.