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

First Author  Miyoshi H Year  2012
Journal  Science Volume  338
Issue  6103 Pages  108-13
PubMed ID  22956684 Mgi Jnum  J:187747
Mgi Id  MGI:5438149 Doi  10.1126/science.1223821
Citation  Miyoshi H, et al. (2012) Wnt5a potentiates TGF-beta signaling to promote colonic crypt regeneration after tissue injury. Science 338(6103):108-13
abstractText  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 Lieberkuhn. 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-beta (TGF-beta) signaling. These findings suggest a Wnt5a-dependent mechanism for forming new crypt units to reestablish homeostasis.
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