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Involvement of RelA-associated inhibitor in regulation of trophoblast differentiation via interaction with transcriptional factor specificity protein-1.
- Source :
-
Endocrinology [Endocrinology] 2007 Dec; Vol. 148 (12), pp. 5803-10. Date of Electronic Publication: 2007 Sep 13. - Publication Year :
- 2007
-
Abstract
- Glucose transporter-1 (GLUT1), one of the key functional indicators of placental differentiation, has an important role in placental glucose transport. We previously showed that the protein levels of GLUT1 and nuclear transcription factor specificity protein-1 (Sp1) in rat choriocarcinoma cells (Rcho-1 cells) decreased during the differentiation of these cells to giant cells. We also showed that Sp1 was involved in the regulation of GLUT1 gene expression during this process. RelA-associated inhibitor (RAI) is an inhibitor of nuclear factor-kappaB that was identified by a yeast two-hybrid screen and is preferably expressed in human placenta and heart. RAI was also found to interact with Sp1 and exert an inhibitory effect against the DNA-binding activity of Sp1. We first show here that RAI mRNA expression increased as gestation proceeded and that RAI was localized mainly in the syncytiotrophoblast throughout pregnancy. The chloramphenicol acetyltransferase activity assay in Rcho-1 cells revealed that cotransfection of RAI expression vector resulted in decreased activity of the rat GLUT1 promoter but not in that of a mutated rat GLUT1 promoter lacking the Sp1 binding site. Furthermore, the protein level of RAI increased during differentiation. In addition, transfection of RAI expression vector promoted the morphological differentiation of Rcho-1 cells, and RAI knockdown using RAI-specific small interfering RNA reveals inhibitory effects on the morphological differentiation, as assessed by photomicroscopy. Taken together, these findings suggest that RAI may be involved in the regulation of trophoblast differentiation via interaction with Sp1.
- Subjects :
- Animals
Blotting, Western
Cell Differentiation genetics
Cell Line, Tumor
Chloramphenicol O-Acetyltransferase genetics
Chloramphenicol O-Acetyltransferase metabolism
Female
Gene Expression Regulation, Developmental
Glucose Transporter Type 1 genetics
Glucose Transporter Type 1 metabolism
Glucose Transporter Type 1 physiology
Humans
Immunohistochemistry
Immunoprecipitation
Intracellular Signaling Peptides and Proteins genetics
Pregnancy
Promoter Regions, Genetic genetics
RNA, Messenger genetics
RNA, Messenger metabolism
RNA, Small Interfering genetics
Rats
Repressor Proteins
Reverse Transcriptase Polymerase Chain Reaction
Sp1 Transcription Factor genetics
Transcription, Genetic
Transfection
Trophoblasts cytology
Cell Differentiation physiology
Intracellular Signaling Peptides and Proteins metabolism
Sp1 Transcription Factor metabolism
Trophoblasts metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0013-7227
- Volume :
- 148
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 17872376
- Full Text :
- https://doi.org/10.1210/en.2007-0142