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Am J Pathol. 2014 Mar;184(3):592-9. doi: 10.1016/j.ajpath.2013.11.029. Epub 2014 Jan 11.

Gut commensal bacteria and regional Wnt gene expression in the proximal versus distal colon.

Author information

  • 1Epithelial Pathobiology and Mucosal Inflammation Research Unit, Emory University, Atlanta, Georgia; Department of General and Visceral Surgery, University of Muenster, Muenster, Germany.
  • 2Epithelial Pathobiology and Mucosal Inflammation Research Unit, Emory University, Atlanta, Georgia; Division of Molecular Embryology, German Cancer Research Center, Heidelberg, Germany.
  • 3Epithelial Pathobiology and Mucosal Inflammation Research Unit, Emory University, Atlanta, Georgia.
  • 4Department of Pharmacology, University of North Carolina,Chapel Hill, Chapel Hill, North Carolina.
  • 5Department of Pediatrics, Emory University, Atlanta, Georgia.
  • 6Department of Infectious Diseases and Pathology, University of Florida, Gainesville, Florida.
  • 7Epithelial Pathobiology and Mucosal Inflammation Research Unit, Emory University, Atlanta, Georgia. Electronic address: anusrat@emory.edu.

Abstract

Regional expression of Wingless/Int (Wnt) genes plays a central role in regulating intestinal development and homeostasis. However, our knowledge of such regional Wnt proteins in the colon remains limited. To understand further the effect of Wnt signaling components in controlling intestinal epithelial homeostasis, we investigated whether the physiological heterogeneity of the proximal and distal colon can be explained by differential Wnt signaling. With the use of a Wnt signaling-specific PCR array, expression of 84 Wnt-mediated signal transduction genes was analyzed, and a differential signature of Wnt-related genes in the proximal versus distal murine colon was identified. Several Wnt agonists (Wnt5a, Wnt8b, and Wnt11), the Wnt receptor frizzled family receptor 3, and the Wnt inhibitory factor 1 were differentially expressed along the colon length. These Wnt signatures were associated with differential epithelial cell proliferation and migration in the proximal versus distal colon. Furthermore, reduced Wnt/β-catenin activity and decreased Wnt5a and Wnt11 expression were observed in mice lacking commensal bacteria, an effect that was reversed by conventionalization of germ-free mice. Interestingly, myeloid differentiation primary response gene 88 knockout mice showed decreased Wnt5a levels, indicating a role for Toll-like receptor signaling in regulating Wnt5a expression. Our results suggest that the morphological and physiological heterogeneity within the colon is in part facilitated by the differential expression of Wnt signaling components and influenced by colonization with bacteria.

Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

PMID:
24418259
[PubMed - in process]
PMCID:
PMC3936305
Free PMC Article
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