Medizinische Universität Graz - Research portal
Selected Publication:
Kulovic, A.
Influence of platelet-derived factors on TGF-β signaling in trophoblast.
[ Diplomarbeit/Master Thesis (UNI) ] Karl-Franzens-Universität Graz; 2022.
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- Authors Med Uni Graz:
- Advisor:
- Gauster Martin
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- Abstract:
- Cytokines and growth factors, including TGF-β, which are expressed in the placenta and released upon platelet activation, may influence trophoblast differentiation and function. Therefore, this thesis aimed to determine the impact of platelet-derived factors on TGF-β signaling, focusing on its downstream target PAI-1 and TGF-β receptor type III (TGFBR3) to elucidate the role of TGFBR3 in the regulation of TGF-β-mediated PAI-1 expression. For that purpose, the trophoblast cell line BeWo was transfected using pre-designed TGFBR3 siRNA prior to platelet lysate- or platelet releasate-treatment in undifferentiated or differentiated cells. Subsequently, gene expression and protein analysis of trophoblast cells were performed in addition to immunohistochemistry and immunofluorescence to assess the localization of TGFBR3 in cells and tissue. TGFBR3 was significantly downregulated on gene and protein expression levels in transfected trophoblast cells, whereas platelet-derived factors did not affect TGFBR3 expression. Placental tissue analysis revealed an increase in TGFBR3 expression towards term in healthy and a downregulation in pathological tissue. Using histological staining methods, TGFBR3 was primarily localized on the apical surface of the syncytiotrophoblast and in vitro in the BeWo cells´ cytoplasmic membrane. Platelet-derived factors significantly induced PAI-1 upregulation, whereas interestingly, PAI-1 expression was not altered upon TGFBR3 silencing in presence or absence of platelet-derived factors in both undifferentiated and differentiated cells. PAI-1 expression increased with gestational age, moreover, an elevated expression was determined in pathological tissue. Based on our in vitro experiments, it may be inferred that TGFBR3 is not directly involved in regulating platelet-derived factor-induced upregulation of PAI-1.