Artículo
Krüppel-like factor 6 (klf6) requires its amino terminal domain to promote villous trophoblast cell fusion
Miranda, Andrea Lis
; Racca, Ana Cristina
; Kourdova, Lucille Tihomirova
; Rojas, Maria Laura
; Cruz del Puerto, Mariano Matias Arzud
; Rodríguez Lombardi, Gonzalo Ramón; Salas, Andrea Verónica; Travella, Claudia; da Silva, Elaine C. O.; de Souza, Samuel T.; Fonseca, Eduardo J. S.; Marques, Aldilane L. X.; Borbely, Alexandre U.; Genti de Raimondi, Susana
; Panzetta-Dutari, Graciela Maria del Valle
Fecha de publicación:
12/2021
Editorial:
W B Saunders Co Ltd
Revista:
Placenta
ISSN:
0143-4004
e-ISSN:
1532-3102
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Introduction: Villous cytotrophoblast (vCTB) cells fuse to generate and maintain the syncytiotrophoblast layer required for placental development and function. Krüppel-like factor 6 (KLF6) is a ubiquitous transcription factor with an N-terminal acidic transactivation domain and a C-terminal zinc finger DNA-binding domain. KLF6 is highly expressed in placenta, and it is required for proper placental development. We have demonstrated that KLF6 is necessary for cell fusion in human primary vCTBs, and in the BeWo cell line. Materials and Methods: Full length KLF6 or a mutant lacking its N-terminal domain were expressed in BeWo cells or in primary vCTB cells isolated from human term placentas. Cell fusion, gene and protein expression, and cell proliferation were analyzed. Moreover, Raman spectroscopy and atomic force microscopy (AFM) were used to identify biochemical, topography, and elasticity cellular modifications. Results: The increase in KLF6, but not the expression of its deleted mutant, is sufficient to trigger cell fusion and to raise the expression of β-hCG, syncytin-1, the chaperone protein 78 regulated by glucose (GRP78), the ATP Binding Cassette Subfamily G Member 2 (ABCG2), and Galectin-1 (Gal-1), all molecules involved in vCTB differentiation. Raman and AFM analysis revealed that KLF6 reduces NADH level and increases cell Young`s modulus. KLF6-induced differentiation correlates with p21 upregulation and decreased cell proliferation. Remarkable, p21 silencing reduces cell fusion triggered by KLF6 and the KLF6 mutant impairs syncytialization and decreases syncytin-1 and β-hCG expression. Discussion: KLF6 induces syncytialization through a mechanism that involves its regulatory transcriptional domain in a p21-dependent manner.
Palabras clave:
PLACENTA
,
KLF6
,
DIFFERENTIATION
,
TROPHOBLAST
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Articulos(CIBICI)
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Citación
Miranda, Andrea Lis; Racca, Ana Cristina; Kourdova, Lucille Tihomirova; Rojas, Maria Laura; Cruz del Puerto, Mariano Matias Arzud; et al.; Krüppel-like factor 6 (klf6) requires its amino terminal domain to promote villous trophoblast cell fusion; W B Saunders Co Ltd; Placenta; 117; 12-2021; 129-149
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