Peptide fragments of AMP-18, a novel secreted gastric antrum mucosal protein, are mitogenic and motogenic.
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.
Toback
F Gary
FG
The Univ. of Chicago, Dept. of Medicine, Chicago, IL 60637, USA. gtoback@medicine.bsd.uchicago.edu
Walsh-Reitz
Margaret M
MM
Musch
Mark W
MW
Chang
Eugene B
EB
Del Valle
John
J
Ren
Hongyu
H
Huang
Erick
E
Martin
Terence E
TE
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005753:Gastric Mucosa / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007422:Intestines / Q000166:cytology; D051379:Mice; D008934:Mitogens / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D036361:Peptide Hormones; D010455:Peptides; D011706:Pyloric Antrum / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D013552:Swine; D014945:Wound Healing
D016861:Cyclooxygenase Inhibitors; C477000:GKN1 protein, human; D008934:Mitogens; D010446:Peptide Fragments; D036361:Peptide Hormones; D010455:Peptides; D005576:Colforsin; D007213:Indomethacin