title: The human leukocyte antigen G promotes trophoblast fusion and β-hCG production through the Erk1/2 pathway in human choriocarcinoma cell lines.
abstract: The human leukocyte antigen G (HLA-G) is expressed on the fetal-maternal interface and plays a role in protecting fetal-derived trophoblasts from the maternal immune response, allowing trophoblasts to invade the uterus. However, HLA-G also possesses immune suppressing-independent functions. We found that HLA-G expressing BeWo choriocarcinoma cells increased cell-cell fusion compared to control BeWo cells under forskolin treatment. Regardless of forskolin treatment, the expression of fusogenic gene mRNAs, including syncytin-1, the transcription factor glial cell missing 1 (Gcm1), and beta human chorionic gonadotropin (β-hCG) were elevated. HLA-G up-regulates β-hCG production in human choriocarcinoma cells because HLA-G knockdown in JEG-3 cells induces a dramatic decrease in β-hCG compared with control cells. The defect in β-hCG production in HLA-G knocked-down cells could not be completely overcome by stimulating hCG production through increasing intracellular cAMP levels. HLA-G expressing cells have increased phosphorylation levels for extracellular signal-regulated kinase1/2 (Erk1/2) in BeWo cells. The Erk1/2 pathway is inactivated after the inhibition of HLA-G expression in JEG-3 cells. Finally, Erk1/2 inhibition was able to suppress the increased hCG production induced by HLA-G expression. Together, these data suggest novel roles for HLA-G in regulating β-hCG production via the modulation of the Erk1/2 pathway and by inducing trophoblast cell fusion.
authors.affiliation: School of Medicine, Nankai University, Tianjin 300071, China.
authors.forename: Ji-meng
authors.initials: JM
authors.lastname: Wang
authors.forename: Hong-xi
authors.initials: HX
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Zhi-ying
authors.initials: ZY
authors.lastname: Gao
authors.forename: Yuan-qing
authors.initials: YQ
authors.lastname: Yao
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D002459:Cell Fusion; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006063:Chorionic Gonadotropin / Q000096:biosynthesis*; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D059951:HLA-G Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D020935:MAP Kinase Signaling System; D060888:Real-Time Polymerase Chain Reaction; D014327:Trophoblasts / Q000166:cytology*; D015854:Up-Regulation
chemical_list: D006063:Chorionic Gonadotropin; D017931:DNA Primers; D059951:HLA-G Antigens