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Heat shock protein-27 (HSP27) regulates STAT3 and eIF4G levels in first trimester human placenta

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Abstract

During placental implantation, cytotrophoblast cells differentiate to extravillous trophoblast (EVT) cells that invade from the placenta into the maternal uterine blood vessels. The heat shock protein-27 (HSP27), the signal transducer and activator of transcription-3 (STAT3) and the eukaryotic translation initiation factor 4E (EIF4E) are involved in regulating EVT cell differentiation/migration. EIF4E and EIF4G compose the translation initiation complex, which is a major control point in protein translation. The molecular chaperone distinctiveness of HSP27 implies that it directly interferes with many target proteins. STAT3, EIF4E, and EIF4G were found to be HSP27 client proteins in tumor cells. We aimed to analyze if HSP27 regulate STAT3 and EIF4G levels in first trimester human placenta. We found that like STAT3, EIF4G is highly expressed in the EVT cells (immunohistochemistry). Silencing HSP27 in HTR-8/SVneo cells (siRNA, EVT cell line) and in placental explants reduced STAT3 level (47 and 33 %, respectively, p < 0.05). HSP27 silencing reduced the levels of STAT3 phosphorylation (33 % reduction, p < 0.05) and targets (IRF1, MUC1, MMP2/9 and EIF4E, 30–49 % reduction, p < 0.05) in the HTR-8/SVneo cells. Moreover, HSP27 silencing significantly reduced EIF4G level and elevated the level of its fragments in HTR-8/SVneo cells and in the placental explants (p < 0.05). In conclusion, Placental implantation and development are accompanied by trophoblast cell proliferation and differentiation, which necessitates intense protein translation and STAT3 activation. HSP27 was found to be regulator of translation initiation and STAT3 level. Therefore, it suggests that HSP27 is a key protein during placental development and trophoblast cell differentiation.

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Acknowledgment

We thank Faye Schreiber for the English editing.

Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

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    Authors and Affiliations

    1. Oncogenetic Laboratory, Meir Medical Centre, 59 Tschernchovski St., 44281, Kfar Saba, Israel

      Gali Epstein Shochet, Oded Komemi, Liat Drucker, Michael Lishner & Shelly Tartakover Matalon

    2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

      Gali Epstein Shochet, Oded Komemi, Dana Sadeh-Mestechkin, Meir Pomeranz, Ami Fishman, Liat Drucker, Michael Lishner & Shelly Tartakover Matalon

    3. Department of Obstetrics and Gynecology, Meir Medical Centre, 44281, Kfar Saba, Israel

      Dana Sadeh-Mestechkin, Meir Pomeranz & Ami Fishman

    4. Department of Internal Medicine A, Meir Medical Centre, 44281, Kfar Saba, Israel

      Michael Lishner

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    1. Gali Epstein Shochet
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    Correspondence to Shelly Tartakover Matalon.

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    Gali Epstein Shochet and Oded Komemi have contributed equally to this work.

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    Shochet, G.E., Komemi, O., Sadeh-Mestechkin, D. et al. Heat shock protein-27 (HSP27) regulates STAT3 and eIF4G levels in first trimester human placenta. J Mol Hist 47, 555–563 (2016). https://doi.org/10.1007/s10735-016-9699-7

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