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MUCOSAL BIOLOGY

Peptide fragments of AMP-18, a novel secreted gastric antrum mucosal protein, are mitogenic and motogenic

Departments of ¹Medicine and ³Molecular Genetics and Cell Biology, The University of Chicago, Chicago, Illinois 60637; and ²Department of Medicine, University of Michigan, Ann Arbor, Michigan 48109

Submitted 23 October 2002 ; accepted in final form 18 March 2003

Antrum mucosal protein (AMP)-18 is a novel 18-kDa protein synthesized by cells of the gastric antrum mucosa. The protein is present in secretion granules of murine gastric antrum epithelial cells and is a component of canine antrum mucus, suggesting that it is secreted into the viscoelastic gel layer on the mucosal surface. Release of the protein appears to be regulated because forskolin decreased the amount of immunoreactive AMP-18 in primary cultures of canine antrum mucosal epithelial cells, and indomethacin gavaged into the stomach of mice reduced AMP-18 content in antrum mucosal tissue before inducing histological injury. A functional domain of the protein was identified by preparing peptides derived from the center of human AMP-18. A 21-mer peptide stimulated growth of gastric and intestinal epithelial cells, but not fibroblasts, and increased restitution of scrape-wounded gastric epithelial monolayers. These functions of AMP-18 suggest that its release onto the apical cell surface is regulated and that the protein and/or peptide fragments may protect the antral mucosa and promote healing by facilitating restitution and proliferation after injury.

growth factor; wound healing; restitution; epithelium; stomach

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