Paradoxical discrepancy between the serum level and the placental intensity of PP5/TFPI-2 in preeclampsia and/or intrauterine growth restriction: possible interaction and correlation with glypican-3 hold the key.
There have been controversies whether maternal serum placental protein 5 (PP5)/tissue factor pathway inhibitor (TFPI)-2 is increased in the patients with preeclampsia and/or intrauterine growth restriction (IUGR). Here, we have estimated the serum PP5/TFPI-2 in these patients by a sandwich enzyme-linked immunosorbent assay with a newly developed monoclonal antibody, coupled with placental immunohistochemical studies of their placentae with semiquantitative scoring. Serum PP5/TFPI-2 level was significantly elevated only in the patients with preeclampsia alone (p=0.033), while PP5/TFPI-2 was detected significantly less intensely in the placentae of the same patients (p=0.035) in immunohistochemistry, as compared to Controls. A proteoglycan present on the placental villous surface, glypican-3, showed the same pattern of staining as PP5/TFPI-2, and there was a positive correlation (C.I.=0.506, p=0.004) between the immunohistochemical scores for these. Further experiments using HepG2 cells transfected with PP5/TFPI-2 suggested that glypican-3 could anchor PP5/TFPI-2 on the placental villi. A possibility that a decrease in glypican-3 in the placenta increases the outflow of PP5/TFPI-2, which in turn increases its serum level, was proposed. Preeclampsia and IUGR, often regarded to have the same pathological basis in common, showed distinct distributions of PP5/TFPI-2, which could be a clue to elucidate the pathogenesis of preeclampsia and IUGR.
Department of Obstetrics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
M
M
Ogawa
S
S
Yanoma
Y
Y
Nagashima
N
N
Okamoto
H
H
Ishikawa
A
A
Haruki
E
E
Miyagi
T
T
Takahashi
F
F
Hirahara
Y
Y
Miyagi
D000328:Adult; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000378:metabolism*; D006023:Glycoproteins / Q000097:blood / Q000378:metabolism*; D053673:Glypicans / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D008297:Male; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000097:blood / Q000378:metabolism*; D011247:Pregnancy; D053668:Syndecan-1 / Q000378:metabolism
D006023:Glycoproteins; D053673:Glypicans; D053668:Syndecan-1; C021240:tissue-factor-pathway inhibitor 2