The Role of heat shock protein 27 in extravillous trophoblast differentiation.
Trophoblast cells from placental explants differentiate in culture to extravillous trophoblast cells (EVT cells). During trophoblast differentiation heat-shock-protein-27 (HSP27) mRNA and multidrug-resistance-protein-5 (MRP5, transporter of cyclic nucleotides) expression are increased. HSP27 is a regulator of actin filaments structure and dynamic, has a role in cell differentiation and may affect NF-kB activity. In this study we aimed to assess HSP27 level in trophoblast cells and its correlation with motility and differentiation related processes [MMPs activity, nitric oxide (NO), inducible nitric oxide synthase (iNOS), proliferation and MRP5 levels]. We evaluated HSP27 expression in a first trimester human trophoblast explants model designed to assess EVT cells differentiation/migration with/without 6-mercaptopurine (6MP, an EVT inhibitor of migration). We found that HSP27 level is expressed in the nucleous and cytoplasm of non-proliferting villous-trophoblast cells (negative for Ki67) and in the cell periphery and cytoplasm of motile EVT cells. Moreover, 6MP decreased HSP27 nucleous expression that was associated with inhibited MMP2 activity and NO production. Also decreased iNOS expression and increased MRP5 mRNA levels were observed. In conclusion, HSP27 expression is modulated in concordance with migration dependent parameters in trophoblast cells.
Matalon
S Tartakover
ST
Oncogenetic Laboratory, Meir Medical Center, Kfar-Saba, Israel. matalon.shelly@clalit.org.il
Drucker
L
L
Fishman
A
A
Ornoy
A
A
Lishner
M
M
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002824:Chorionic Villi / Q000378:metabolism / Q000648:ultrastructure*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D015122:Mercaptopurine / Q000494:pharmacology; D018832:Molecular Chaperones; D016328:NF-kappa B / Q000096:biosynthesis; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012333:RNA, Messenger / Q000096:biosynthesis; D014327:Trophoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*
D018435:ATP Binding Cassette Transporter, Subfamily B; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D019394:Ki-67 Antigen; D018832:Molecular Chaperones; D016328:NF-kappa B; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D015122:Mercaptopurine; D020778:Matrix Metalloproteinase 2