title: The effect of heat shock protein 27 on extravillous trophoblast differentiation and on eukaryotic translation initiation factor 4E expression.
abstract: Heat shock protein (HSP27) is expressed in human placentae. Previously, we showed that HSP27 is expressed in the villous cell column of first trimester placental explants and in extravillous trophoblast (EVT) cells. EVT differentiation is accompanied by increased motility, matrix metalloproteinase (MMP) activity, decreased proliferation and expression of specific markers such as HLAG and CD9. HSP27 regulates cell apoptosis, migration, protein stability and the availability of eukaryotic translation initiation factors, such as eukaryotic translation initiation factor 4E (eIF4E). eIF4E supports trophoblast cell proliferation and survival. We wanted to explore the effect of HSP27 silencing on trophoblast cell phenotype, EVT markers and eIF4E expression and regulators [4E-binding protein (4E-BP1) and MAP kinase-interacting kinase (MNK1)]. This study evaluated the effect of HSP27 siRNA on placental explant and HTR-8/SVneo migration, MMP activity/mRNA, cell death, cell cycle, HLAG/CD9 levels, and eIF4E and its regulators' total and phosphorylated levels. Furthermore, we evaluated HSP27 levels in placentae exposed to ribavirin, which triggers EVT differentiation. We found that HSP27 silencing increased cell death in HTR-8/SVneo and placental explants. Furthermore, it reduced HTR-8/SVneo migration and EVT outgrowth from the explants (P < 0.05), MMP2 activity and expression of EVT markers HLAG and CD9 (in placental explants and HTR-8/SVneo, respectively, P < 0.05). Induction of EVT differentiation by ribavirin elevated HSP27 levels. Finally, HSP27 silencing in both HTR-8/SVneo and placental explants reduced eIF4E levels (33 and 28%, respectively, P < 0.05) and the levels of its regulators 4E-BP1 and MNK1 (37 and 32%, respectively, done on HTR-8/SVneo only), but not their phosphorylated forms. Altogether, our results suggest that HSP27 contributes to EVT cell differentiation.
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Sadeh-Mestechkin
authors.forename: G
authors.initials: G
authors.lastname: Epstein Shochet
authors.forename: M
authors.initials: M
authors.lastname: Pomeranz
authors.forename: A
authors.initials: A
authors.lastname: Fishman
authors.forename: L
authors.initials: L
authors.lastname: Drucker
authors.forename: T
authors.initials: T
authors.lastname: Biron-Shental
authors.forename: M
authors.initials: M
authors.lastname: Lishner
authors.forename: S
authors.initials: S
authors.lastname: Tartakover Matalon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D018797:Cell Cycle Proteins; D016923:Cell Death; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D059951:HLA-G Antigens / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012254:Ribavirin / Q000494:pharmacology; D015398:Signal Transduction; D060245:Tetraspanin 29 / Q000378:metabolism; D013997:Time Factors; D046509:Tissue Culture Techniques; D014162:Transfection; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C554869:CD9 protein, human; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D039561:Eukaryotic Initiation Factor-4E; D059951:HLA-G Antigens; D055551:HSP27 Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D060245:Tetraspanin 29; D012254:Ribavirin; C491395:MKNK1 protein, human; D017346:Protein Serine-Threonine Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: HSP27; differentiation; eIF4E; placenta