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Protein kinase CK2 contributes to placental development: physiological and pathological implications

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Abstract

Preeclampsia (PE) is the most threatening pathology of human pregnancy. Its development is thought to be due to a failure in the invasion of trophoblast cells that establish the feto-maternal circulation. Protein kinase CK2 is a ubiquitous enzyme reported to be involved in the control of cell invasion. CK2 consists of two subunits, a catalytic subunit, CK2α, and a regulatory subunit, CK2β. To date, no data exist regarding the expression and role of this enzyme in normal and PE pregnancies. We performed studies, at the clinical level using distinctive cohorts from early pregnancy (n = 24) and from PE (n = 23) and age-matched controls (n = 28); in vitro, using trophoblast cell lines; ex vivo, using placental explants; and in vivo, using PE mouse models. We demonstrated that (i) CK2 is more expressed during the late first trimester of pregnancy and is mainly localized in differentiated trophoblast cells, (ii) the inhibition of its enzymatic activity decreased the proliferation, migration, invasion, and syncytialization of trophoblast cells, both in 2D and 3D culture systems, and (iii) CK2 activity and the CK2α/CK2β protein ratio were increased in PE human placentas. The pattern and profile of CK2 expression were confirmed in gravid mice along with an increase in the PE mouse models. Altogether, our results demonstrate that CK2 plays an essential role in the establishment of the feto-maternal circulation and that its deregulation is associated with PE development. The increase in CK2 activity in PE might constitute a compensatory mechanism to ensure proper pregnancy progress.

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Acknowledgments

We also thank Ms. Sophie Ndagijimana and Ms. Aude Salomon for their technical assistance.

Funding information

We acknowledge the following sources of fundings: Institut National de la Santé et de la Recherche Médicale (U1036), University Grenoble-Alpes, Commissariat à l’Energie Atomique (DRF/IRIG/BCI), Région Auvergne-Rhône-Alpes “CLARA”, Ligue Nationale contre le Cancer and Ligue Départementale (Isère) and Fondation pour la recherche Médicale (FRM) SPF20150934074.

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Correspondence to Roland Abi Nahed.

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Abi Nahed, R., Reynaud, D., Lemaitre, N. et al. Protein kinase CK2 contributes to placental development: physiological and pathological implications. J Mol Med 98, 123–133 (2020) doi:10.1007/s00109-019-01855-0

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Keywords

  • Placenta
  • Protein kinase CK2
  • Preeclampsia
  • Animal model
  • Trophoblast invasion