Prokineticin 1 is up-regulated by insulin in decidualizing human endometrial stromal cells

Dorina Ujvari, Ivika Jakson, Cecilia Oldmark, Sanaz Attarha, Twana Alkasalias, D. Salamon, Sebastian Gidlöf, Angelica Lindén Hirschberg

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Prokineticin 1 (PROK1), a hypoxia-regulated angiogenic factor, has emerged as a crucial regulator of embryo implantation and placentation. Dysregulation of PROK1 has been linked to recurrent pregnancy loss, pre-eclampsia, foetal growth restriction and preterm birth. These pregnancy complications are common in women with obesity and polycystic ovary syndrome, i.e. conditions associated with insulin resistance and compensatory hyperinsulinaemia. We investigated the effect of insulin on PROK1 expression during in vitro decidualization. Endometrial stromal cells were isolated from six healthy, regularly menstruating women and decidualized in vitro. Insulin induced a significant dose-dependent up-regulation of PROK1 on both mRNA and protein level in decidualizing endometrial stromal cells. This up-regulation was mediated by hypoxia-inducible factor 1-alpha (HIF1α) via the phosphatidylinositol 3-kinase (PI3K) pathway. Furthermore, we demonstrated that PROK1 did not affect the viability, but significantly inhibited the migration of endometrial stromal cells and the migratory and invasive capacity of trophoblast cell lines. This in vitro study provides new insights into the regulation of PROK1 by insulin in human decidualizing endometrial stromal cells, the action of PROK1 on migration of endometrial stromal cells, as well as migration and invasion of trophoblasts. We speculate that hyperinsulinaemia may be involved in the mechanisms by which PROK1 is linked to placenta-related pregnancy complications.

Original languageEnglish
Pages (from-to)163-172
Number of pages10
JournalJournal of Cellular and Molecular Medicine
Volume22
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

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Endocrine-Gland-Derived Vascular Endothelial Growth Factor
Stromal Cells
Insulin
Pregnancy Complications
Trophoblasts
Hyperinsulinism
Up-Regulation
Phosphatidylinositol 3-Kinase
Hypoxia-Inducible Factor 1
Placentation
Angiogenesis Inducing Agents
Polycystic Ovary Syndrome
Premature Birth
Fetal Development
Pre-Eclampsia
Placenta
Insulin Resistance
Obesity

Keywords

  • decidualization
  • EG-VEGF
  • endometrium
  • insulin
  • invasion
  • migration
  • PROK1
  • trophoblast

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

Cite this

Prokineticin 1 is up-regulated by insulin in decidualizing human endometrial stromal cells. / Ujvari, Dorina; Jakson, Ivika; Oldmark, Cecilia; Attarha, Sanaz; Alkasalias, Twana; Salamon, D.; Gidlöf, Sebastian; Hirschberg, Angelica Lindén.

In: Journal of Cellular and Molecular Medicine, Vol. 22, No. 1, 01.01.2018, p. 163-172.

Research output: Contribution to journalArticle

Ujvari, D, Jakson, I, Oldmark, C, Attarha, S, Alkasalias, T, Salamon, D, Gidlöf, S & Hirschberg, AL 2018, 'Prokineticin 1 is up-regulated by insulin in decidualizing human endometrial stromal cells', Journal of Cellular and Molecular Medicine, vol. 22, no. 1, pp. 163-172. https://doi.org/10.1111/jcmm.13305
Ujvari, Dorina ; Jakson, Ivika ; Oldmark, Cecilia ; Attarha, Sanaz ; Alkasalias, Twana ; Salamon, D. ; Gidlöf, Sebastian ; Hirschberg, Angelica Lindén. / Prokineticin 1 is up-regulated by insulin in decidualizing human endometrial stromal cells. In: Journal of Cellular and Molecular Medicine. 2018 ; Vol. 22, No. 1. pp. 163-172.
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