Successful placental implantation is essential for healthy fetal growth. During implantation cytotrophoblast cells proliferate and differentiate to extravillous trophoblast cells (EVT).
Elevated levels of heat shock protein 27 (HSP27) were found in EVT cells and in preeaclamptic (PET) placentae. HSP27 has several important functions including protection from apoptosis and modulation of cell migration. Lately, we demonstrated an elevated eIF4E level (eukaryotic translation initiation factor 4E) in differentiating EVT cells.
EIF4E prevents final EVT cell differentiation and supports placental cell proliferation and survival. Its level is balanced by stabilizing factors such as HSP27.
Objective: Analyzing the involvement of HSP27 in EVT cell function and its effect on eIF4E expression.
Study Design: We evaluated the effect of HSP27 knockdown (siRNA) on 1) EVT cell line (HTR-8/SVNEO) death (Annexin/7AAD, flow-cytometry (FACS)), cell-cycle (PI, FACS), migration (Scratch) and eIF4E level (WB).
Results: HSP27 silencing significantly inhibited HTR-8/SVNEO cell migration, elevated their cell-death (220% elevation) and the SUB-G1 phase of their cell cycle (44% elevation), which also support cell death (all P<0.05). Moreover, silencing HSP27 significantly reduced eIF4E level (50% reduction, P<0.05) and its phosphorylated form (36% reduction, P<0.05).
Conclusion: Our results show that HSP27 regulates eIF4E levels in an EVT model and its silencing deleteriously affects cell survival and migration. The observation of the HSP27-eIF4E-phenotype axis in EVT cells is novel. PET placentae represent elevated apoptosis and blight protein translation. Thus, we put forward that the elevated level of HSP27 in PET placentae may represent a defense mechanism against these malfunctions.
Tartakover-Matalon S1,3, Sadeh-Mestechkin D1,2, ,Pomeranz M2,3, Fishman A2,3, Epstein Shochet G1,3, Drucker L1,3, Lishner M1,3
Oncogenetic Laboratory1 and Department of Obstetrics & Gynecology2, Meir Medical Center, Sackler Faculty of Medicine3, Tel-Aviv University, Israel.