The possible role of the PK1 and its receptor in the etiology of the preeclampsia.

OBJECTIVE: Preeclampsia (PE) is a hypertensive complication of the pregnancy. In our study we investigated the expression, localization, and signaling pathways of PK1 and PKR1 in third-trimester human placenta and myometrium and assessed the correlation between the PK1 and PKR1 expression and signaling and the incidence of the PE. MATERIALS & METHODS: We designed two study groups: pregnant PE patients and healthy, pregnant women. After collection, tissue was placed in RNAlater for RNA extraction, fixed in 4% neutral buffered formalin, and wax embedded for immunohistochemistry or placed in RPMI and transported to the laboratory for in vitro culture. We have collected and processed placental and myometrial biopsies from 40 patients - 19 were PE patients. RESULTS: Only the PK1 mRNA expression comparison between PE and CTRL in placenta showed statistically significant difference (p=0.004). There was statistically significant difference in cell signaling in myometrium controls in 30 minutes after ligand. The rise in pERK/tERK ratio is clearly visible in time intervals 20 and 30 minutes in controls, although with no statistical significance. There was no difference in PK1 and PKR1 localization in the placenta and myometrium in the groups. CONCLUSIONS: The number of PKR1 is not reduced in PE. The reduced PK1 mRNA expression is not than dependent on PKR1 mRNA expression. The data shows that ST produces much more PK1 in healthy pregnant women than those suffering from PE. We can conclude that in PE the production of PK1 is impaired and so are the endocrine functions of the ST.

Prokineticin-1: a novel mediator of the inflammatory response in third-trimester human placenta.

Prokineticin-1 (PK1) is a recently described protein with a wide range of functions, including tissue-specific angiogenesis, modulation of inflammatory responses, and regulation of hemopoiesis. The aim of this study was to investigate the localization and expression of PK1 and PK receptor-1 (PKR1), their signaling pathways, and the effect of PK1 on expression of the inflammatory mediators cyclooxygenase (COX)-2 and IL-8 in third-trimester placenta. PK1 and PKR1 were highly expressed in term placenta and immunolocalized to syncytiotrophoblasts, cytotrophoblasts, fetal endothelium, and macrophages. PK1 induced a time-dependent increase in expression of IL-8 and COX-2, which was significantly reduced by inhibitors of Gq, cSrc, epidermal growth factor receptor (EGFR), and MAPK kinase. Treatment of third-trimester placenta with 40 nm PK1 induced a rapid phosphorylation of cSrc, EGFR, and ERK1/2. Phosphorylation of ERK1/2 in response to PK1 was dependent on sequential phosphorylation of cSrc and EGFR. Using double-immunofluorescent immunohistochemistry, PKR1 colocalized with IL-8 and COX-2 in placenta. These data suggest that PK1 may have a novel role as a mediator of the inflammatory response in placenta.