Hepatocyte growth factor activator (HGF-A) and its zymogen in human placenta

HGF-activator (HGF-A) is a circulating serine protease known to be responsi ble for activation of hepatocyte growth factor (HGF). Active HGF is thought to be an important regulator of trophoblast growth. In vitro, HGF-A is pro duced via proteolytic cleavage of its zymogen by thrombin. Immunocytochemis try and Western immunoblotting were performed using human placental tissue from all three trimesters with an antibody that recognizes both HGF-A and i ts zymogen. Western immunoblotting revealed a 97 kDa band equivalent to the zymogen in placenta from all three trimesters. A smaller 34 kDa band equiv alent to HGF-A was only seen in first and second trimester placenta. The an ti-HGF-A/zymogen antibody demonstrated immunostaining in placental villi an d membranes throughout gestation. Within first trimester villi immunostaini ng was strongest within the syncytio- and cytotrophoblast layers, but was a lso seen within stromal and endothelial cells. Likewise, in third trimester placenta the syncytio-cytotrophoblast layer showed the strongest immunorea ctivity. In vitro, HGF can induce trophoblast DNA synthesis and the localiz ation of HGF-A to the peri-villous trophoblast layer (which expresses c-met , the HGF receptor) suggests that it may be responsible for activation of p ro-HGF at this site. This adds further weight to the hypothesis that HGF in vivo is an important regulator of trophoblast growth. (C) 2000 Harcourt Pu blishers Ltd.