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

Ewa Mlyczyńska , Patrycja Kurowska , Eliza Drwal , Małgorzata Opydo‑Chanek , Wacław Tworzydło , Małgorzata Kotula-Balak , Agnieszka Rak


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.
Author Ewa Mlyczyńska - Jagiellonian University (UJ)
Ewa Mlyczyńska,,
, Patrycja Kurowska - Jagiellonian University (UJ)
Patrycja Kurowska,,
, Eliza Drwal - Jagiellonian University (UJ)
Eliza Drwal,,
, Małgorzata Opydo‑Chanek - Jagiellonian University (UJ)
Małgorzata Opydo‑Chanek,,
, Wacław Tworzydło - Jagiellonian University (UJ)
Wacław Tworzydło,,
, Małgorzata Kotula-Balak (VET)
Małgorzata Kotula-Balak,,
- University Centre for Veterinary Medicine UJ-UR
, Agnieszka Rak - Jagiellonian University (UJ)
Agnieszka Rak,,
Journal seriesInternational Journal of Molecular Medicine, ISSN 1107-3756, e-ISSN 1791-244X, (N/A 70 pkt)
Issue year2020
Publication size in sheets0.55
Keywords in Englishapelin, proliferation, cell cycle, signal transduction, placenta
ASJC Classification2700 General Medicine; 1311 Genetics
URL https://www.spandidos-publications.com/10.3892/ijmm.2020.4452/download
Languageen angielski
LicenseJournal (articles only); author's original; Uznanie Autorstwa - Użycie Niekomercyjne - Bez utworów zależnych (CC-BY-NC-ND); after publication
Apelin and apelin receptor in human placenta: Expression, signalling pathway and regulation of trophoblast JEG‑3 and BeWo cells proliferation and cell cycle of 02-04-2020
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Score (nominal)70
Score sourcejournalList
Publication indicators WoS Citations = 1; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 0.827; WoS Impact Factor: 2018 = 2.928 (2) - 2018=2.843 (5)
Citation count*
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FinansowanieThe present study was supported by the Jagiellonian University (grant no. K/ZdS/008063). The cost of Open Access publication was covered by the Society for Biology of Reproduction in Poland.
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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