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NPFF increases fusogenic proteins syncytin 1 and syncytin 2 via GCM1 in first trimester primary human cytotrophoblast cells
Author(s) -
Zhu Hua,
Peng Bo,
Klausen Christian,
Yi Yuyin,
Li Yan,
Xiong Siyuan,
Dadelszen Peter,
Leung Peter C. K.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201902978r
Subject(s) - cytotrophoblast , downregulation and upregulation , gene knockdown , placenta , trophoblast , placentation , andrology , microbiology and biotechnology , chemistry , biology , pregnancy , gene , fetus , medicine , genetics , biochemistry
Neuropeptide FF (NPFF) is well‐known for its roles in the central nervous system. Despite studies demonstrating that NPFF receptor 2 (NPFFR2) mRNA is highest in placenta, nothing is known about NPFF‐NPFFR2 functions in placental development. Here, we investigated the effects of NPFF‐NPFFR2 on expression of syncytial [human chorionic gonadotropin (hCG) β] and fusogenic [syncytin 1, syncytin 2, and glial cells missing 1 (GCM1)] genes in first trimester primary human cytotrophoblast cells. By analyzing two publicly available microarray data sets, we found that NPFF is consistently expressed throughout gestation whereas NPFFR2 increases in first trimester and is elevated in placenta samples from women with preeclampsia. Immunohistochemistry showed that NPFFR2, syncytin 1/2, and GCM1 each displayed unique patterns of expression among different trophoblast populations in first trimester placenta. Treatment of primary human cytotrophoblast cells with NPFF increased the mRNA and protein levels of hCG β, syncytin 1, syncytin 2, and GCM1; and knockdown of NPFFR2 abolished these effects. Interestingly, GCM1 mediated NPFF‐induced upregulation of syncytin 1 and syncytin 2, but not hCG β, in primary human cytotrophoblasts. Our results demonstrate that NPFF acts via NPFFR2 to enhance production of hCG β and promote GCM1‐dependent expression of syncytin 1 and 2 in human cytotrophoblasts.