title: MSX2 Induces Trophoblast Invasion in Human Placenta.
abstract: Normal implantation depends on appropriate trophoblast growth and invasion. Inadequate trophoblast invasion results in pregnancy-related disorders, such as early miscarriage and pre-eclampsia, which are dangerous to both the mother and fetus. Msh Homeobox 2 (MSX2), a member of the MSX family of homeobox proteins, plays a significant role in the proliferation and differentiation of various cells and tissues, including ectodermal organs, teeth, and chondrocytes. Recently, MSX2 was found to play important roles in the invasion of cancer cells into adjacent tissues via the epithelial-mesenchymal transition (EMT). However, the role of MSX2 in trophoblastic invasion during placental development has yet to be explored. In the present study, we detected MSX2 expression in cytotrophoblast, syncytiotrophoblast, and extravillous cytotrophoblast cells of first or third trimester human placentas via immunohistochemistry analysis. Furthermore, we found that the in vitro invasive ability of HTR8/SVneo cells was enhanced by exogenous overexpression of MSX2, and that this effect was accompanied by increased protein expression of matrix metalloproteinase-2 (MMP-2), vimentin, and β-catenin. Conversely, treatment of HTR8/SVneo cells with MSX2-specific siRNAs resulted in decreased protein expression of MMP-2, vimentin, and β-catenin, and reduced invasion levels in a Matrigel invasion test. Notably, however, treatment with the MSX2 overexpression plasmid and the MSX2 siRNAs had no effect on the mRNA expression levels of β-catenin. Meanwhile, overexpression of MSX2 and treatment with the MSX2-specific siRNA resulted in decreased and increased E-cadherin expression, respectively, in JEG-3 cells. Lastly, the protein expression levels of MSX2 were significantly lower in human pre-eclamptic placental villi than in the matched control placentas. Collectively, our results suggest that MSX2 may induce human trophoblast cell invasion, and dysregulation of MSX2 expression may be associated with pre-eclampsia.
authors.affiliation: Laboratory Animal Center, Chongqing Medical University, Chongqing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liang
authors.affiliation: Laboratory Animal Center, Chongqing Medical University, Chongqing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Laboratory Animal Center, Chongqing Medical University, Chongqing, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Lu
authors.affiliation: Laboratory Animal Center, Chongqing Medical University, Chongqing, China.
authors.forename: Genling
authors.initials: G
authors.lastname: Yang
authors.affiliation: Laboratory Animal Center, Chongqing Medical University, Chongqing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Tian
authors.affiliation: Laboratory Animal Center, Chongqing Medical University, Chongqing, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratory Animal Center, Chongqing Medical University, Chongqing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Laboratory Animal Center, Chongqing Medical University, Chongqing, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Tan
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002824:Chorionic Villi / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D010929:Placentation; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000378:metabolism / Q000473:pathology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D018398:Homeodomain Proteins; C084119:MSX2 protein; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051176:beta Catenin