title: Hepatocyte growth factor activator (HGF-A) and its zymogen in human placenta.
abstract: HGF-activator (HGF-A) is a circulating serine protease known to be responsible for activation of hepatocyte growth factor (HGF). Active HGF is thought to be an important regulator of trophoblast growth. In vitro, HGF-A is produced via proteolytic cleavage of its zymogen by thrombin. Immunocytochemistry and Western immunoblotting were performed using human placental tissue from all three trimesters with an antibody that recognizes both HGF-A and its zymogen. Western immunoblotting revealed a 97 kDa band equivalent to the zymogen in placenta from all three trimesters. A smaller 34 kDa band equivalent to HGF-A was only seen in first and second trimester placenta. The anti-HGF-A/zymogen antibody demonstrated immunostaining in placental villi and membranes throughout gestation. Within first trimester villi immunostaining was strongest within the syncytio- and cytotrophoblast layers, but was also seen within stromal and endothelial cells. Likewise, in third trimester placenta the syncytio-cytotrophoblast layer showed the strongest immunoreactivity. In vitro, HGF can induce trophoblast DNA synthesis and the localization 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 pro-HGF at this site. This adds further weight to the hypothesis that HGF in vivo is an important regulator of trophoblast growth.
authors.affiliation: Department of Fetal Medicine, Division of Reproductive and Child Health, Birmingham Women's Hospital, University of Birmingham, B15 2TG, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Somerset
authors.forename: A J
authors.initials: AJ
authors.lastname: Strain
authors.forename: S
authors.initials: S
authors.lastname: Afford
authors.forename: M J
authors.initials: MJ
authors.lastname: Whittle
authors.forename: M D
authors.initials: MD
authors.lastname: Kilby
mesh_terms: D015153:Blotting, Western; D004792:Enzyme Precursors / Q000032:analysis* / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D012697:Serine Endopeptidases / Q000032:analysis* / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D014327:Trophoblasts / Q000201:enzymology
chemical_list: D004792:Enzyme Precursors; C081092:HGF activator; D012697:Serine Endopeptidases; D013917:Thrombin