M. Kolatsijoannou et al., EXPRESSION OF HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR AND ITS RECEPTOR, MET, SUGGESTS ROLES IN HUMAN EMBRYONIC ORGANOGENESIS, Pediatric research, 41(5), 1997, pp. 657-665
Hepatocyte growth factor/scatter factor (HGF/SF) is secreted by mesenc
hymal cells and elicits proliferation, motility, differentiation, and
morphogenesis of epithelia and other cells. These effects are mediated
by binding to MET, a receptor tyrosine kinase. Genetically engineered
mice lacking HGF/SF die in utero due to a failure of placental and he
patocyte differentiation, but little information exists regarding the
expression of this signaling system in human development. Using revers
e transcriptase-polymerase chain reaction, Western blots, and immunohi
stochemistry, we report that HGF/SF and MET are expressed during criti
cal early periods of human organogenesis from 6 to 13 wk of gestation.
Organs that expressed both genes included liver, metanephric kidney,
intestine, and lung, each of which develop by inductive interactions b
etween mesenchyme and epithelia. Of all organs studied, the placenta c
ontained the highest levels of HGF/SF protein, and MET was detected in
trophoblastic cells of chorionic villi as early as the 5th wk of gest
ation. Finally, examination of a human multicystic dysplastic kidney d
emonstrated that malformed, hyperproliferative tubules expressed MET,
whereas HGF/SF protein was immunolocalized to the same epithelia and a
lso to the surrounding undifferentiated cells. Hence HGF/SF might be a
n important growth factor in normal human embryogenesis and may additi
onally play a role in human organ malformations.