Homeobox gene TGIF-1 is increased in placental endothelial cells of human fetal growth restriction.
Reproduction
; 152(5): 457-65, 2016 11.
Article
em En
| MEDLINE
| ID: mdl-27539603
ABSTRACT
Aberrant placental angiogenesis is associated with fetal growth restriction (FGR). In mice, targeted disruption of the homeobox gene, transforming growth ß-induced factor (Tgif-1), which is also a transcription factor, causes defective placental vascularisation. Nevertheless, the role of TGIF-1 in human placental angiogenesis is unclear. We have previously reported increased TGIF-1 expression in human FGR placentae and demonstrated localisation of TGIF-1 protein in placental endothelial cells (ECs). However, its functional role remains to be investigated. In this study, we aimed to specifically compare TGIF-1 mRNA expression in placental ECs isolated from human FGR-affected pregnancies with gestation-matched control pregnancies in two independent cohorts from Australia and Canada and to identify the functional role of TGIF-1 in placental angiogenesis using the human umbilical vein endothelial cell-derived cell line, SGHEC-7, and primary human umbilical vein ECs. Real-time PCR revealed that TGIF-1 mRNA expression was significantly increased in ECs isolated from FGR-affected placentae compared with that of controls. The functional roles of TGIF-1 were determined in ECs after TGIF-1 siRNA transfection. TGIF-1 inactivation in ECs significantly reduced TGIF-1 at both the mRNA and protein levels, as well as the proliferative and invasive potential, but significantly increased the angiogenic potential. Using angiogenesis PCR screening arrays, we identified ITGAV, NRP-1, ANPGT-1 and ANPGT-2 as novel downstream targets of TGIF-1, after TGIF-1 inactivation in ECs. Collectively, these results show that TGIF-1 regulates EC function and the expression of angiogenic molecules; and when abnormally expressed, may contribute to the aberrant placental angiogenesis observed in FGR.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Placenta
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Proteínas Repressoras
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Trofoblastos
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Proteínas de Homeodomínio
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Células Endoteliais
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Retardo do Crescimento Fetal
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Female
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Humans
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Infant
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Male
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Pregnancy
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article