Functional characterization of the keratinocyte growth factor system in human fetal gastrointestinal tract

Keratinocyte growth factor (KGF) is a paracrine growth factor whose mRNA ha s been detected in human adult and rodent gut tissues together with its ass ociated receptor. Our objectives were to assess the presence of immunoreact ive KGF ligand and receptor proteins in human fetal gastrointestinal (GI) t ract segments and to evaluate the role of exogenous KGF on cell proliferati on and intestinal digestive functions. KGF (26-28 kD doublet) was identifie d in esophagus, stomach, small intestine, and colon by Western blot. Its re ceptor (135 kD) was ubiquitously detected in proliferative and differentiat ed epithelial cells of each GI segment by use of indirect immunofluorescenc e (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-glut amyl-transpeptidase activities in jejunal exp]ants, whereas it down-regulat ed 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 diffe rentially regulate intestinal digestive functions.