title: Wnt5a potentiates TGF-β signaling to promote colonic crypt regeneration after tissue injury.
abstract: Reestablishing homeostasis after tissue damage depends on the proper organization of stem cells and their progeny, though the repair mechanisms are unclear. The mammalian intestinal epithelium is well suited to approach this problem, as it is composed of well-delineated units called crypts of Lieberkühn. We found that Wnt5a, a noncanonical Wnt ligand, was required for crypt regeneration after injury in mice. Unlike controls, Wnt5a-deficient mice maintained an expanded population of proliferative epithelial cells in the wound. We used an in vitro system to enrich for intestinal epithelial stem cells to discover that Wnt5a inhibited proliferation of these cells. Surprisingly, the effects of Wnt5a were mediated by activation of transforming growth factor-β (TGF-β) signaling. These findings suggest a Wnt5a-dependent mechanism for forming new crypt units to reestablish homeostasis.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Rieko
authors.initials: R
authors.lastname: Ajima
authors.forename: Christine T
authors.initials: CT
authors.lastname: Luo
authors.forename: Terry P
authors.initials: TP
authors.lastname: Yamaguchi
authors.forename: Thaddeus S
authors.initials: TS
authors.lastname: Stappenbeck
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003106:Colon / Q000196:embryology / Q000293:injuries* / Q000502:physiology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D007413:Intestinal Mucosa / Q000196:embryology / Q000293:injuries / Q000502:physiology; D008024:Ligands; D008648:Mesoderm / Q000166:cytology / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D000071818:Wnt-5a Protein; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
chemical_list: D017077:Culture Media, Conditioned; D008024:Ligands; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; D013629:Tamoxifen; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; C477010:Ror2 protein, mouse