Gut Commensal Bacteria and Regional Wnt Gene Expression in the Proximal Versus Distal Colon

• Authors: Philipp Neumann, Emory University; Stefan Koch, Emory University; Roland Hilgarth, Emory University; Ernesto Perez-Chanona, University of North Carolina; Patricia Denning, Emory University; Christian Jobin, University of Florida; Asma Nusrat, Emory University
• Journal Title: American Journal of Pathology
• Volume: Volume 184, Number 3
• Publisher: American Society for Investigative Pathology (ASIP) | 2014-03-01, Pages 592-599
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1016/j.ajpath.2013.11.029
• Subjects: Health Sciences, Pathology; Health Sciences, Pharmacology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Pathology; PATHOLOGY; INTESTINAL EPITHELIAL-CELLS; COLORECTAL-CANCER; NONCANONICAL WNT; PANETH CELLS; MICROBIOTA; DISEASE; PROLIFERATION; HOMEOSTASIS; ACTIVATION; RECEPTORS

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.