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Regulation of stanniocalcin-1 secretion by BeWo cells and first trimester human placental tissue from normal pregnancies and those at increased risk of developing preeclampsia.

Abid, N; Embola, J; Tryfonos, Z; Bercher, J; Ashton, SV; Khalil, A; Thilaganathan, B; Cartwright, JE; Whitley, GS (2020) Regulation of stanniocalcin-1 secretion by BeWo cells and first trimester human placental tissue from normal pregnancies and those at increased risk of developing preeclampsia. FASEB J, 34 (5). pp. 6086-6098. ISSN 1530-6860 https://doi.org/10.1096/fj.201902426R
SGUL Authors: Whitley, Guy St John Cartwright, Judith Eleanor Khalil, Asma

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Abstract

Stanniocalcin-1 (STC-1) is a multi-functional glycosylated peptide present in the plasma of healthy women postpartum and increased further in pregnancies complicated by preeclampsia. Although the STC-1 gene is expressed by the placenta what regulates its secretion and from which cells at the feto-maternal interface is unknown. Here, we demonstrate for the first time that the syncytiotrophoblast and cytotrophoblast are a major site of STC-1 protein expression in first trimester placental tissue. Further, in response to low oxygen, first trimester chorionic villous tissue from pregnancies at increased risk of developing preeclampsia secreted significantly more STC-1 than normal tissue under the same conditions. Using the human trophoblast cell line BeWo we have shown that low oxygen increased the secretion of STC-1 but it required co-stimulation with the Adenosine-3', 5'-cyclic monophosphate (cAMP) analogue, 8-Bromo adenosine-3', 5'-cyclic monophosphate cAMP (8 Br-cAMP) to reach significance. Inhibition of Hypoxia inducible factor 2α (HIF-2α) and the Phosphatidylinositol-3 kinase (PI3 -Kinase)/AKT/Serum and glucocorticoid-induced kinase-1(SGK-1) pathway resulted in significant inhibition of STC-1 secretion. As both low oxygen and cAMP are known to play a central role in placental function, their regulation of STC-1 points to a potentially important role in the maintenance of a normal healthy pregnancy and we would hypothesize that it may act to protect against prolonged placental hypoxia seen in preeclampsia.

Item Type: Article
Additional Information: © 2020 The Authors. The FASEB Journal published by Wiley Periodicals, Inc. on behalf of Federation of American Societies for Experimental Biology This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: first trimester, hypoxia, placenta, stanniocalcin-1, trophoblasts, Biochemistry & Molecular Biology, 0601 Biochemistry and Cell Biology, 0606 Physiology, 1116 Medical Physiology
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: FASEB J
ISSN: 1530-6860
Language: eng
Dates:
DateEvent
4 May 2020Published
12 March 2020Published Online
3 February 2020Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
MR/M02184X/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
UNSPECIFIEDSociety for Reproduction and Fertilityhttp://dx.doi.org/10.13039/501100000593
UNSPECIFIEDHigher Education Funding Council for Englandhttp://dx.doi.org/10.13039/501100000384
PubMed ID: 32162740
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/111747
Publisher's version: https://doi.org/10.1096/fj.201902426R

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