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Wnt5a potentiates TGF-β signaling to promote colonic crypt regeneration after tissue injury.

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.

Pubmed ID: 22956684

Authors

  • Miyoshi H
  • Ajima R
  • Luo CT
  • Yamaguchi TP
  • Stappenbeck TS

Journal

Science (New York, N.Y.)

Publication Data

October 5, 2012

Associated Grants

  • Agency: NIDDK NIH HHS, Id: 5T35DK074375
  • Agency: NIDDK NIH HHS, Id: DK90251
  • Agency: NIDDK NIH HHS, Id: P30-DK52574
  • Agency: NIDDK NIH HHS, Id: R01 DK071619
  • Agency: Intramural NIH HHS, Id:

Mesh Terms

  • Animals
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Colon
  • Culture Media, Conditioned
  • Homeostasis
  • Intestinal Mucosa
  • Ligands
  • Mesoderm
  • Mice
  • Mice, Knockout
  • Receptor Tyrosine Kinase-like Orphan Receptors
  • Recombinant Proteins
  • Signal Transduction
  • Stem Cells
  • Tamoxifen
  • Transforming Growth Factor beta
  • Wnt Proteins
  • Wound Healing