Increased levels of pregnancy-associated plasma protein-A2 in the serum of pre-eclamptic patients.
Pregnancy-associated plasma protein-A and -A2 (PAPP-A and -A2) are proteases that cleave insulin-like growth factor-binding proteins (IGFBPs), resulting in local activation of IGF signaling pathways. Here, we examined PAPP-A and -A2 mRNA and protein levels in placenta and maternal sera from women with pre-eclampsia and compared them with samples from uncomplicated pregnancy. PAPP-A2 but not PAPP-A mRNA and protein were elevated in pre-eclamptic placenta (P < 0.01). PAPP-A2 is normally produced in placental syncytiotrophoblast cells and maternal decidua. PAPP-A2 in syncytiotrophoblast cells was dramatically increased in pre-eclampsia. Maternal serum concentrations of PAPP-A2 but not PAPP-A were also significantly elevated in pre-eclampsia as compared with uncomplicated pregnancy. mRNA levels of IGFBP5, a specific substrate for PAPP-A2 protease activity, were also significantly increased, suggesting a potential role for IGFBP5 in fetal and placental growth suppression during pre-eclampsia. However, IGFBP5 protein levels were not increased in placenta from pre-eclampsia, possibly due to cleavage by up-regulated PAPP-A2. These data might imply that PAPP-A2 may be up-regulated in pre-eclamptic pregnancy to compensate for IGFBP5-mediated suppression of the IGF pathway, although final birthweights are still low in pre-eclamptic pregnancy.
Nishizawa
Haruki
H
Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan. nharuki@fujita-hu.ac.jp
Pryor-Koishi
Kanako
K
Suzuki
Machiko
M
Kato
Takema
T
Kogo
Hiroshi
H
Sekiya
Takao
T
Kurahashi
Hiroki
H
Udagawa
Yasuhiro
Y
D000328:Adult; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005865:Gestational Age; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000097:blood* / Q000235:genetics; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018975:Insulin-Like Growth Factor Binding Protein 5; C430889:PAPPA2 protein, human; D011266:Pregnancy-Associated Plasma Protein-A