title: Relevance of Wnt10b and activation of β-catenin/GCMa/syncytin-1 pathway in BeWo cell fusion.
abstract: OBJECTIVE
  To study the involvement of specific Wnt(s) ligand during trophoblastic BeWo cell differentiation.
  
  
  METHODS
  BeWo cells on treatment with forskolin/human chorionic gonadotropin (hCG) were studied for cell fusion by desmoplakin I+II staining and/or hCG secretion by ELISA. Levels of Wnt10b/β-catenin/glial cell missing a (GCMa)/syncytin-1 were studied by qPCR/Western blotting in forskolin-/hCG-treated control siRNA and Wnt10b silenced BeWo cells.
  
  
  RESULTS
  BeWo cells on treatment with hCG (5 IU/mL) led to a 94-fold increase in Wnt10b transcript. Wnt10b silencing showed significant decrease in forskolin-/hCG-mediated BeWo cell fusion and/or hCG secretion. It led to down-regulation of β-catenin (nuclear and cytoplasmic), GCMa and syncytin-1 expression. Treatment of BeWo cells with H89, protein kinase A (PKA) signaling inhibitor, significantly reduced forskolin-/hCG-induced Wnt10b, β-catenin, and syncytin-1 expression, which also resulted in reduced cell fusion.
  
  
  CONCLUSIONS
  Wnt10b is involved in forskolin/hCG-mediated BeWo cell fusion via β-catenin/GCMa/syncytin pathway, which may also involve activation of PKA.
authors.affiliation: Reproductive Cell Biology Laboratory, National Institute of Immunology, New Delhi, India.
authors.forename: Sudha Saryu
authors.initials: SS
authors.lastname: Malhotra
authors.affiliation: Reproductive Cell Biology Laboratory, National Institute of Immunology, New Delhi, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Banerjee
authors.affiliation: Reproductive Cell Biology Laboratory, National Institute of Immunology, New Delhi, India.
authors.forename: Piyush
authors.initials: P
authors.lastname: Chaudhary
authors.affiliation: Immunoendocrinology Laboratory, National Institute of Immunology, New Delhi, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Pal
authors.affiliation: Reproductive Cell Biology Laboratory, National Institute of Immunology, New Delhi, India.
authors.forename: Satish Kumar
authors.identifier: http://orcid.org/0000-0003-3717-0436
authors.initials: SK
authors.lastname: Gupta
mesh_terms: D002454:Cell Differentiation; D002459:Cell Fusion; D045744:Cell Line, Tumor; D006063:Chorionic Gonadotropin / Q000378:metabolism; D005576:Colforsin / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins; D051180:Desmoplakins / Q000378:metabolism; D015686:Gene Products, env / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D011257:Pregnancy Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D004268:DNA-Binding Proteins; D051180:Desmoplakins; C491089:GCM1 protein, human; D015686:Gene Products, env; D009687:Nuclear Proteins; D011257:Pregnancy Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; C491119:WNT10B protein, human; D051153:Wnt Proteins; D051176:beta Catenin; C405335:syncytin; D005576:Colforsin; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Canonical β-catenin signaling; PKA signaling; forskolin/human chorionic gonadotropin-mediated BeWo cell fusion