DEVELOPMENTAL EXPRESSION AND FUNCTIONALITY OF HEPATOCYTE GROWTH-FACTOR AND C-MET IN HUMAN FETAL DIGESTIVE TISSUES

Background & Aims: Hepatocyte growth factor (HGF) and its receptor c-M et are presumed to play a morphogenic role during embryogenesis. The p ossible implication of HGF and c-Met during the digestive system devel opment was approached by investigating their ontogeny, distribution, a nd functionality in human fetal tissues. Methods: Thirty fetuses, 7-24 weeks old, were obtained. HGF and c-Met messenger RNAs and proteins w ere detected in liver, pancreas, esophagus, stomach, and small and lar ge intestine. Tyrosine phosphorylation assays were realized on homogen ates and membrane preparations from fetal tissues. Results: The tempor al appearance of HGF and c-Met was established between 7 and 8 weeks o f gestation in digestive tissues. Immunoblot analysis showed the prese nce of the c-Met beta-subunit 145-kilodalton band and of the HGF cc-su bunit 70-kilodalton band. c-Met was localized in epithelia, especially in fundic parietal cells, pancreatic and gut endocrine cells, and in muscular layers. HGF immunoreactivity was first detected in epithelia and then in mesenchyme and muscular layers. In young fetal stages, the c-Met immunoprecipitated 145-kilodalton band showed tyrosine phosphor ylation after HGF stimulation. Conclusions: This study provides eviden ce for HGF and c-Met expression early in all human fetal digestive tis sues and implicates HGF-c-Met in the digestive system morphogenesis.