GLP-2 stimulates colonic growth via KGF, released by subepithelial myofibroblasts with GLP-2 receptors.

TY - JOUR

T1 - GLP-2 stimulates colonic growth via KGF, released by subepithelial myofibroblasts with GLP-2 receptors.

AU - Ørskov, Cathrine

AU - Hartmann, Bolette

AU - Poulsen, Steen Seier

AU - Thulesen, Jesper

AU - Hare, Kristine Juul

AU - Holst, Jens Juul

N1 - Keywords: Actins; Animals; Cell Proliferation; Colon; Female; Fibroblast Growth Factor 7; Fibroblast Growth Factors; Fibroblasts; Glucagon-Like Peptide 2; Glucagon-Like Peptides; Humans; Mice; Peptides; Rats; Receptors, Glucagon

PY - 2005

Y1 - 2005

N2 - 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. METHODS AND 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.

AB - 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. METHODS AND 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.

U2 - 10.1016/j.regpep.2004.07.009

DO - 10.1016/j.regpep.2004.07.009

M3 - Journal article

C2 - 15544847

SN - 0167-0115

VL - 124

SP - 105

EP - 112

JO - Regulatory Peptides

JF - Regulatory Peptides

IS - 1-3

ER -