Modulation of specific intestinal epithelial progenitors by enteric neurons
- Department of Anatomy and Cell Biology, Medical Sciences Building, University of Toronto, Toronto, ON, Canada M5S 1A8
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Edited by Jeffrey I. Gordon, Washington University School of Medicine, St. Louis, MO, and approved August 22, 2001 (received for review June 4, 2001)
Abstract
The proglucagon-derived peptide glucagon-like peptide 2 (GLP-2), a product of a subset of gut epithelial cells, is pursued clinically for its ability to stimulate gut epithelial growth and repair. Here we show that although specific epithelial progenitors respond to GLP-2 administration, the epithelium does not express the GLP-2 receptor. Rather, enteric neurons express the receptor, respond to GLP-2, and transmit a signal (which can be blocked by the voltage-gated sodium channel inhibitor tetrodotoxin) back to the epithelium. Thus the nervous system is a key component of a feedback loop regulating epithelial growth and repair.
Footnotes
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↵ * To whom reprint requests should be addressed. E-mail: matthew.bjerknes{at}utoronto.ca.
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This paper was submitted directly (Track II) to the PNAS office.
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See commentary on page 12334.
- Abbreviations:
- GLP-2,
- glucagon-like peptide 2;
- Glp-2r, GLP-2 receptor gene,
- ISH, in situ hybridization;
- KGF,
- keratinocyte growth factor;
- NEU,
- N-ethyl-N-nitrosourea;
- TTX,
- tetrodotoxin;
- DIG,
- digoxigenin;
- GFAP,
- glial fibrillary acidic protein
- Copyright © 2001, The National Academy of Sciences
