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Published on: November 8, 2024
PLAC1 expression increases during trophoblast differentiation: evidence for regulatory interactions with the
Eltayab Massabbal1, Shanaz Parveen, D L Weisoly
1Department of Pediatrics, University of Texas--Houston Medical School, Houston, Texas 77030, USA.
Insights
The placental-specific gene PLAC1 is upregulated during trophoblast differentiation, localizing to the syncytiotrophoblast. Peptide growth factors like FGF-7 regulate PLAC1 expression via specific signaling pathways.
Area of Science:
- Reproductive biology
- Developmental biology
- Genetics
Background:
- PLAC1 is a trophoblast-specific gene located on the X-chromosome, implicated in placental development.
- Immunohistochemistry reveals PLAC1 polypeptide localization in syncytiotrophoblast throughout gestation and in a subset of villous cytotrophoblasts.
Purpose of the Study:
- To investigate the expression pattern and regulation of PLAC1 during trophoblast differentiation.
- To identify specific growth factors and signaling pathways involved in PLAC1 regulation.
Main Methods:
- Quantitative RT-PCR to measure PLAC1 mRNA levels during cytotrophoblast differentiation.
- Treatment of BeWo(b30) trophoblast cell line with growth factors (FGF-7, EGF) and inhibitors (PD-98059, wortmannin).
- Immunohistochemical analysis of PLAC1 and FGFR-2b expression in placental tissue.
Main Results:
- PLAC1 mRNA increased over 300-fold during in vitro cytotrophoblast differentiation into syncytiotrophoblasts.
- Fibroblast growth factor-7 (FGF-7) stimulated PLAC1 mRNA expression twofold, mediated by MAP kinase and PI-3 kinase pathways.
- Epidermal growth factor (EGF) potentiated FGF-7's effect, indicating a regulatory interaction.
Conclusions:
- PLAC1 expression is significantly upregulated during trophoblast differentiation, primarily in the syncytiotrophoblast.
- Peptide growth factors, particularly FGF-7, play a specific role in regulating PLAC1 expression through defined signaling cascades.
- The interaction between FGF-7 and EGF suggests complex regulatory mechanisms governing PLAC1 during placental development.
Abstract:
PLAC1 is a recently described, trophoblast-specific gene that localizes to a region of the X-chromosome important in placental development. Immunohistochemical analysis demonstrated that PLAC1 polypeptide localizes to the differentiated syncytiotrophoblast throughout gestation (8-41 weeks) as well as a small population of villous cytotrophoblasts. Consistent with these observations, quantitative RT-PCR demonstrated that PLAC1 mRNA increases more than 300-fold during cytotrophoblast differentiation in culture to form syncytiotrophoblasts. Agents known to be relevant to trophoblast differentiation were then tested for the ability to influence PLAC1 expression. Fibroblast growth factor-7 (FGF-7), also known as keratinocyte growth factor (KGF), stimulated PLAC1 mRNA expression approximately two-fold in the BeWo(b30) trophoblast cell line. FGF-7 stimulation was significantly inhibited by PD-98059 and wortmannin suggesting mediation via MAP kinase and PI-3 kinase-dependent signaling pathways. Interestingly, epidermal growth factor (EGF) treatment of trophoblasts had no effect on PLAC1 expression alone, but potentiated the effect of FGF-7, suggesting the presence of a regulatory interaction of the two growth factors. FGF-7 and its receptor, FGFR-2b, exhibited spatial overlap with PLAC1 suggesting these regulatory interactions are physiologically relevant during gestation. These data demonstrate PLAC1 expression is upregulated during trophoblast differentiation, localizing primarily to the differentiated syncytiotrophoblast. Furthermore PLAC1 expression is specifically regulated by peptide growth factors relevant to trophoblast differentiation.
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