Wnt signaling is boosted during intestinal regeneration by a CD44-positive feedback loop.

Date publication

février 2022

Journal

Cell death & disease

Auteurs

Membres identifiés du Cancéropôle Est :
Pr MELY Yves , Dr RICHERT Ludovic

Tous les auteurs :
Walter RJ, Sonnentag SJ, Munoz-Sagredo L, Merkel M, Richert L, Bunert F, Heneka YM, Loustau T, Hodder M, Ridgway RA, Sansom OJ, Mely Y, Rothbauer U, Schmitt M, Orian-Rousseau V

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/35190527

Résumé

Enhancement of Wnt signaling is fundamental for stem cell function during intestinal regeneration. Molecular modules control Wnt activity by regulating signal transduction. CD44 is such a positive regulator and a Wnt target gene. While highly expressed in intestinal crypts and used as a stem cell marker, its role during intestinal homeostasis and regeneration remains unknown. Here we propose a CD44 positive-feedback loop that boosts Wnt signal transduction, thus impacting intestinal regeneration. Excision of Cd44 in Cd44;VillinCreER mice reduced Wnt target gene expression in intestinal crypts and affected stem cell functionality in organoids. Although the integrity of the intestinal epithelium was conserved in mice lacking CD44, they were hypersensitive to dextran sulfate sodium, and showed more severe inflammation and delayed regeneration. We localized the molecular function of CD44 at the Wnt signalosome, and identified novel DVL/CD44 and AXIN/CD44 complexes. CD44 thus promotes optimal Wnt signaling during intestinal regeneration.

Référence

Cell Death Dis. 2022 Feb 21;13(2):168