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PMID: 22956684 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

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

Science (New York, N.Y.) ·Vol. 338 ·No. 6103 ·2012-10-05 ·Pages 108-13

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

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.

MeSH Terms
Animals Cell Movement/drug effects,physiology Cell Proliferation/drug effects Cells, Cultured Colon/embryology,injuries,physiology Culture Media, Conditioned/pharmacology Homeostasis/drug effects,physiology Intestinal Mucosa/embryology,injuries,physiology Ligands Mesoderm/cytology,embryology Mice Mice, Knockout Receptor Tyrosine Kinase-like Orphan Receptors/metabolism Recombinant Proteins/pharmacology Signal Transduction Stem Cells/cytology,drug effects,physiology Tamoxifen/pharmacology Transforming Growth Factor beta/metabolism Wnt Proteins/genetics,pharmacology,physiology Wnt-5a Protein Wound Healing/drug effects,physiology
Chemicals
Culture Media, Conditioned Ligands Recombinant Proteins Transforming Growth Factor beta Wnt Proteins Wnt-5a Protein Wnt5a protein, mouse Tamoxifen Receptor Tyrosine Kinase-like Orphan Receptors Ror2 protein, mouse
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Miyoshi Hiroyuki
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Ajima Rieko
Luo Christine T
Yamaguchi Terry P
Stappenbeck Thaddeus S
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1223821
Published
2012-10-05
Epub
2012-00-06
Pages
108-13
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3706630
Subset
IM
Grants
NIDDK NIH HHS · DK90251 · United States
NIDDK NIH HHS · R01 DK071619 · United States
NIDDK NIH HHS · 5T35DK074375 · United States
NIDDK NIH HHS · P30 DK052574 · United States
NIDDK NIH HHS · T35 DK074375 · United States
NIDDK NIH HHS · P30-DK52574 · United States
Intramural NIH HHS · United States
Corrections
CommentIn
PMID: 23042874
External Links
PubMed source DOI: 10.1126/science.1223821 PMC Full Text View journal details
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