Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Berghold, VM; Gauster, M; Hemmings, DG; Moser, G; Kremshofer, J; Siwetz, M; Sundl, M; Huppertz, B.
Phospholipid scramblase 1 (PLSCR1) in villous trophoblast of the human placenta.
Histochem Cell Biol. 2015; 143(4):381-396
Doi: 10.1007/s00418-014-1294-y
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Berghold Veronika Marlies
- Huppertz Berthold
- Co-Autor*innen der Med Uni Graz
- Gauster Martin
- Kremshofer Julia
- Moser Gerit
- Siwetz Monika
- Sundl Monika
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- Abstract:
- A crucial factor for effective villous trophoblast fusion in the human placenta is the transient deregulation of plasma membrane phospholipid asymmetry leading to externalization of phosphatidylserine to the outer membrane leaflet. Screening of scramblase family members implicated in the collapse of phospholipid asymmetry revealed that phospholipid scramblase 1 (PLSCR1) is strongly expressed in villous trophoblast. Therefore, we assessed the putative role of PLSCR1 in villous trophoblast fusion. Spatio-temporal analysis in first trimester and term placenta showed abundant expression of PLSCR1 in syncytiotrophoblast, macrophages and endothelial cells, while it was virtually absent in villous cytotrophoblasts. For functional studies, BeWo cells, isolated primary term trophoblasts and first trimester villous explants were used. During forskolin-mediated BeWo cell differentiation, neither PLSCR1 mRNA nor protein levels showed significant changes. In contrast, when primary trophoblasts were stimulated with Br-cAMP, a decrease in PLSCR1 mRNA and protein expression was observed. To elucidate a role for PLSCR1 in syncytialization, we used RNA interference and a chemical scramblase inhibitor, R5421 (ethanedioic acid). Silencing of PLSCR1 using siRNA had no effects while inhibition of scramblase activity by R5421 increased GCM-1 mRNA expression, beta-hCG protein secretion and fusion rates of BeWo cells. In primary trophoblasts and villous explants, no effects of siRNA or R5421 treatment on fusion were detected. This study provides data on PLSCR1 localization and general expression in the human placenta. The data make it tempting to speculate on a role of PLSCR1 in negatively regulating trophoblast fusion.
- Find related publications in this database (using NLM MeSH Indexing)
- Cell Differentiation -
- Cell Fusion -
- Cell Line -
- Chorionic Gonadotropin - metabolism
- Enzyme Inhibitors - pharmacology
- Female -
- Gene Expression Regulation, Developmental -
- Gene Expression Regulation, Enzymologic -
- Humans -
- Nuclear Proteins - genetics
- Nuclear Proteins - metabolism
- Phospholipid Transfer Proteins - antagonists & inhibitors
- Phospholipid Transfer Proteins - genetics
- Phospholipid Transfer Proteins - metabolism
- Pregnancy -
- Pregnancy Trimester, First -
- RNA Interference -
- Signal Transduction -
- Time Factors -
- Transcription Factors - genetics
- Transcription Factors - metabolism
- Transfection -
- Trophoblasts - drug effects
- Trophoblasts - enzymology
- Find related publications in this database (Keywords)
- Human placenta
- Phospholipid scramblase 1 (PLSCR1)
- Villous trophoblast fusion
- BeWo
- Scramblase inhibitor R5421