Functional characterization of the keratinocyte growth factor system in human fetal gastrointestinal tract.
Keratinocyte growth factor (KGF) is a paracrine growth factor whose mRNA has been detected in human adult and rodent gut tissues together with its associated receptor. Our objectives were to assess the presence of immunoreactive KGF ligand and receptor proteins in human fetal gastrointestinal (GI) tract segments and to evaluate the role of exogenous KGF on cell proliferation and intestinal digestive functions. KGF (26-28 kD doublet) was identified in esophagus, stomach, small intestine, and colon by Western blot. Its receptor (135 kD) was ubiquitously detected in proliferative and differentiated epithelial cells of each GI segment by use of indirect immunofluorescence (anti-bek, anti-K-sam). The addition of KGF to explants cultured in serum-free conditions greatly stimulated DNA synthesis in all GI tract tissues. The growth factor up-regulated intestinal sucrase-isomaltase and gamma-glutamyl-transpeptidase activities in jejunal explants, whereas it down-regulated these activities in colon explants. It is suggested that the KGF system likely represents an important paracrine pathway that is able to stimulate cell proliferation in all segments of the human fetal GI tract and to differentially regulate intestinal digestive functions.
Chailler
P
P
MRC Group on the Functional Development and Physiopathology of the Digestive Tract, Department of Anatomy and Cell Biology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Québec, Canada.
Basque
J R
JR
Corriveau
L
L
Ménard
D
D
D015153:Blotting, Western; D003106:Colon / Q000737:chemistry / Q000196:embryology / Q000201:enzymology; D046508:Culture Techniques; D004247:DNA / Q000096:biosynthesis; D004064:Digestive System / Q000737:chemistry / Q000196:embryology*; D004847:Epithelial Cells / Q000737:chemistry; D004947:Esophagus / Q000737:chemistry / Q000196:embryology; D005260:Female; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D019084:Fluorescent Antibody Technique, Indirect; D005865:Gestational Age; D006133:Growth Substances / Q000032:analysis* / Q000494:pharmacology; D006801:Humans; D007421:Intestine, Small / Q000737:chemistry / Q000196:embryology; D007583:Jejunum / Q000201:enzymology; D011247:Pregnancy; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor / Q000032:analysis; D013270:Stomach / Q000737:chemistry / Q000196:embryology; D013394:Sucrase-Isomaltase Complex / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
C496453:FGF7 protein, human; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D004247:DNA; D005723:gamma-Glutamyltransferase; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor; D013394:Sucrase-Isomaltase Complex