Open Access

Apelin and apelin receptor in human placenta: Expression, signalling pathway and regulation of trophoblast JEG‑3 and BeWo cells proliferation and cell cycle

  • Authors:
    • Ewa Mlyczyńska
    • Patrycja Kurowska
    • Eliza Drwal
    • Małgorzata Opydo‑Chanek
    • Wacław Tworzydło
    • Małgorzata Kotula‑Balak
    • Agnieszka Rak
  • View Affiliations

  • Published online on: January 7, 2020     https://doi.org/10.3892/ijmm.2020.4452
  • Pages: 691-702
  • Copyright: © Mlyczyńska et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Placentation requires the production of numerous growth factors, hormones and transcription factors. Many of them, like the adipose tissue‑derived leptin or adiponectin, have been identified in the placenta and their role has been established in the proliferation and subsequent development of the placenta. Apelin is another adipokine known for proliferative effects in different cell types. PCR, immunoblotting and immunocytochemistry were used to study mRNA and protein expression of apelin and its receptor (APJ) in syncytiotrophoblast (BeWo) and cytotrophoblast (JEG‑3) cells as well in immunohistochemistry in human normal placenta slides. The effect of apelin on cell proliferation study was investigated by alamarBlue® and Cell Counting Kit‑8 assays, the cell cycle by the flow cytometry method and the protein expression of cyclins and phosphorylation level of extracellular signal‑regulated kinases (ERK)1/2, phosphatidylinositol 3'‑kinase/protein kinase B (Akt), signal transducer and activator of transcription 3 (Stat3) and 5'‑monophosphate‑activated protein kinase (AMPKα) were studied by western blotting. Apelin was increased in JEG‑3 compared with in BeWo cells, while APJ was the same in both placenta cell lines. Immunocytochemical analyses revealed high cytoplasmic and/or membrane apelin localisation in JEG‑3, while BeWo cells exhibited markedly weaker apelin signal in the cytoplasm. Apelin increased cell proliferation as well as the percentage of cells in the G2/M phase of the cell cycle, cyclin proteins and the expression of all kinases mentioned above. In conclusion, apelin by promotion of trophoblast cell proliferation by APJ and ERK1/2, Stat3 and AMPKα signalling could be a new important adipokine in the regulation of early placental development.
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March 2020
Volume 45 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Mlyczyńska, E., Kurowska, P., Drwal, E., Opydo‑Chanek, M., Tworzydło, W., Kotula‑Balak, M., & Rak, A. (2020). Apelin and apelin receptor in human placenta: Expression, signalling pathway and regulation of trophoblast JEG‑3 and BeWo cells proliferation and cell cycle. International Journal of Molecular Medicine, 45, 691-702. https://doi.org/10.3892/ijmm.2020.4452
MLA
Mlyczyńska, E., Kurowska, P., Drwal, E., Opydo‑Chanek, M., Tworzydło, W., Kotula‑Balak, M., Rak, A."Apelin and apelin receptor in human placenta: Expression, signalling pathway and regulation of trophoblast JEG‑3 and BeWo cells proliferation and cell cycle". International Journal of Molecular Medicine 45.3 (2020): 691-702.
Chicago
Mlyczyńska, E., Kurowska, P., Drwal, E., Opydo‑Chanek, M., Tworzydło, W., Kotula‑Balak, M., Rak, A."Apelin and apelin receptor in human placenta: Expression, signalling pathway and regulation of trophoblast JEG‑3 and BeWo cells proliferation and cell cycle". International Journal of Molecular Medicine 45, no. 3 (2020): 691-702. https://doi.org/10.3892/ijmm.2020.4452