GLP-2 stimulates colonic growth via KGF, released by subepithelial myofibroblasts with GLP-2 receptors.
BACKGROUND
Glucagon-like peptide-2 is thought to act as a growth factor for the gut, but the localization of the GLP-2 receptor and mechanism of action on epithelial growth is unclear.


RESULTS
We found glucagon-like peptide-2 (GLP-2) receptors mainly on subepithelial myofibroblasts in rat, mouse, marmoset and human small and large intestine by immunohistochemistry and in situ hybridisation. By double labelling we found that these GLP-2 receptor immunoreactive cells also produce smooth muscle actin and keratinocyte growth factor (KGF). By subcutaneous infusion of either GLP-2 alone, GLP-2 plus KGF antibody, KGF antibody alone or saline in mice, we found that KGF antibody abolished the growth promoting effect of GLP-2 in the large intestine, but not in the small intestine.


CONCLUSIONS
Our findings suggest that GLP-2 in the gut acts by activating receptors on the subepithelial myofibroblasts, causing the release of growth factors, which in turn stimulate intestinal growth.
Ørskov
Cathrine
C
Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Blegdamsvej 3c, Copenhagen DK-2200, Denmark. c.orskov@mai.ku.dk
Hartmann
Bolette
B
Poulsen
Steen Seier
SS
Thulesen
Jesper
J
Hare
Kristine Juul
KJ
Holst
Jens Juul
JJ
D000199:Actins / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D005260:Female; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D053767:Glucagon-Like Peptide 2; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides; D006801:Humans; D051379:Mice; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D018027:Receptors, Glucagon / Q000378:metabolism*
D000199:Actins; C496453:FGF7 protein, human; C496454:Fgf7 protein, mouse; C496455:Fgf7 protein, rat; C000593833:GLP1R protein, human; C000593834:Glp1r protein, mouse; C000593835:Glp1r protein, rat; D053767:Glucagon-Like Peptide 2; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D018027:Receptors, Glucagon; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D004763:Glucagon-Like Peptides