Developmental expression and functionality of hepatocyte growth factor and c-Met in human fetal digestive tissues.
OBJECTIVE
Hepatocyte growth factor (HGF) and its receptor c-Met are presumed to play a morphogenic role during embryogenesis. The possible implication of HGF and c-Met during the digestive system development was approached by investigating their ontogeny, distribution, and functionality in human fetal tissues.


METHODS
Thirty fetuses, 7-24 weeks old, were obtained. HGF and c-Met messenger RNAs and proteins were detected in liver, pancreas, esophagus, stomach, and small and large intestine. Tyrosine phosphorylation assays were realized on homogenates and membrane preparations from fetal tissues.


RESULTS
The temporal appearance of HGF and c-Met was established between 7 and 8 weeks of gestation in digestive tissues. Immunoblot analysis showed the presence of the c-Met beta-subunit 145-kilodalton band and of the HGF alpha-subunit 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 phosphorylation after HGF stimulation.


CONCLUSIONS
This study provides evidence for HGF and c-Met expression early in all human fetal digestive tissues and implicates HGF-c-Met in the digestive system morphogenesis.
Kermorgant
S
S
Unité de Biologie et Pathologie de l'Epithélium Digestif, INSERM Unité 10, IFR Cellules Epithéliales, Hôpital Bichat-Claude Bernard, Paris, France.
Walker
F
F
Hormi
K
K
Dessirier
V
V
Lewin
M J
MJ
Lehy
T
T
D004064:Digestive System / Q000196:embryology*; D004622:Embryo, Mammalian / Q000378:metabolism* / Q000502:physiology*; D005314:Embryonic and Fetal Development; D005865:Gestational Age; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D010766:Phosphorylation; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D014018:Tissue Distribution; D014443:Tyrosine / Q000378:metabolism
D014443:Tyrosine; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases