Wnt5a potentiates TGF-β signaling to promote colonic crypt regeneration after tissue injury.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 22956684.
- Also identified by DOI 10.1126/science.1223821 and PMC identifier 3706630.
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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.
Medical subject headings
- Animals
- Cell Movement
- Cell Movement/drug effects
- Cell Movement/physiology
- Cell Proliferation
- Cell Proliferation/drug effects
- Cells, Cultured
- Colon
- Colon/embryology
- Colon/injuries
- Colon/physiology
- Culture Media, Conditioned
- Culture Media, Conditioned/pharmacology
- Homeostasis
- Homeostasis/drug effects
- Homeostasis/physiology
- Intestinal Mucosa
- Intestinal Mucosa/embryology
- Intestinal Mucosa/injuries
- Intestinal Mucosa/physiology
- Ligands
- Mesoderm
- Mesoderm/cytology
- Mesoderm/embryology
- Mice
- Mice, Knockout
- Receptor Tyrosine Kinase-like Orphan Receptors
- Receptor Tyrosine Kinase-like Orphan Receptors/metabolism
- Recombinant Proteins
- Recombinant Proteins/pharmacology
- Signal Transduction
- Stem Cells
- Stem Cells/cytology
- Stem Cells/drug effects
- Stem Cells/physiology
- Tamoxifen
- Tamoxifen/pharmacology
- Transforming Growth Factor beta
- Transforming Growth Factor beta/metabolism
- Wnt Proteins
- Wnt Proteins/genetics
- Wnt Proteins/pharmacology
- Wnt Proteins/physiology
- Wnt-5a Protein
- Wound Healing
- Wound Healing/drug effects
- Wound Healing/physiology