Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Kremshofer, J.
The role of the G protein-coupled receptor 55 (GPR55) in human placental endothelial cells
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Graz Medical University; 2015. pp. 73
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- Autor*innen der Med Uni Graz:
- Kremshofer Julia
- Betreuer*innen:
- Gauster Martin
- Huppertz Berthold
- Schicho Rudolf
- Altmetrics:
- Abstract:
- The endocannabinoid system (ECS) with its G protein-coupled receptors plays important roles throughout the human body. The system is also suggested to play a key role in human pregnancy, which includes processes like implantation, decidualization, placentation and labor. One particular receptor – the G protein-coupled receptor 55 (GPR55) – was previously postulated to be another cannabinoid receptor, because specific cannabinoids were found to act independently of the two classical cannabinoid receptors CB1 and CB2. Nonetheless, studies revealed great differences between the structure of these two receptors and GPR55. Even if GPR55 can be partly activated by certain endocannabinoids, its main agonist is the lysophospholipid L-a-lysophosphatidylinositol (LPI). Both GPR55 and LPI are known to be part of important pathways in the human body. Nonetheless, knowledge about the role of this receptor during pregnancy and placental development is limited, which motivated me to focus on this topic. In this study aims were the analysis of GPR55 expression in human placenta and the comparison to other human peripheral tissues. Furthermore, evaluation of spatiotemporal human placental GPR55 expression was one important aspect. Analysis of the gene expression profile via qPCR showed that GPR55 levels in human placenta are relatively low compared to tissues with highest receptor expression, which are spleen and lung. When comparing first trimester and term placenta, the latter revealed a 5.8 fold higher expression. Localization of GPR55 via immunohistochemistry determined endothelial cells in first trimester and term placenta to be the only cells expressing the receptor. Strongest expression was found in endothelial cells of small vessels right underneath the trophoblast layer. Larger vessels revealed differential expression in arteries and veins, while umbilical cord vessels only showed very weak GPR55 expression. Receptor expression in endothelial cells was confirmed by immunocytochemistry of isolated primary placental arterial (PAEC) and venous endothelial cells (PVEC). These cells were also used for cell culture experiments analyzing the influence of LPI on endothelial cell functions. Incubation with LPI at a concentration of 1 µM significantly enhanced migration of venous, but not arterial endothelial cells. This LPI-induced migration was partly reduced by the GPR55 antagonist O-1918, leading to the suggestion that the GPR55/LPI axis might play a role in placental venous endothelial cell functions.