Gene regulation of neurokinin B and its receptor NK3 in late pregnancy and pre-eclampsia.
Elevated circulating levels of the tachykinin, neurokinin B (NKB), have been observed in women with pre-eclampsia during the third trimester of pregnancy. Currently, the molecular mechanisms responsible for these increased levels remain unknown. To understand the molecular regulation, we have compared the differences in gene expression of the tachykinins and their receptors in control and pre-eclamptic placentae and the responses of the TAC3 gene encoding NKB to proposed physiological triggers of pre-eclampsia including hypoxia and oxidative stress using real-time quantitative PCR. We have determined the placenta to be the main site of TAC3 expression with levels 2.6-fold higher than the brain. TAC3 expression was found to be significantly higher in pre-eclamptic placenta (1.7-fold, P < 0.05) than in normal controls. No evidence was found that hypoxia and oxidative stress were responsible for increases in TAC3 expression. In rat placenta, a longitudinal study in normal late pregnancy was associated with a significant down-regulation of the NKB/NK3 ligand-receptor pair (P < 0.05). The present data suggest that the increased placental expression of TAC3 is part of the mechanism leading to the increased circulating levels of NKB in pre-eclampsia.
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N M
NM
School of Life Sciences, Kingston University London, Penrhyn Road, Kingston-upon-Thames, Surrey, UK. n.page@kingston.ac.uk
Dakour
J
J
Morrish
D W
DW
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D015287:Neurokinin B / Q000235:genetics*; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011264:Pregnancy Trimesters; D051381:Rats; D018042:Receptors, Neurokinin-3 / Q000235:genetics*; D018039:Receptors, Tachykinin / Q000235:genetics; D015320:Tachykinins / Q000235:genetics; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism
D018042:Receptors, Neurokinin-3; D018039:Receptors, Tachykinin; D015320:Tachykinins; D015287:Neurokinin B