Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Loegl, J; Nussbaumer, E; Hiden, U; Majali-Martinez, A; Ghaffari-Tabrizi-Wizy, N; Cvitic, S; Lang, I; Desoye, G; Huppertz, B.
Pigment epithelium-derived factor (PEDF): a novel trophoblast-derived factor limiting feto-placental angiogenesis in late pregnancy.
Angiogenesis. 2016; 19(3):373-388
Doi: 10.1007/s10456-016-9513-x
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- Führende Autor*innen der Med Uni Graz
- Hiden Ursula
- Co-Autor*innen der Med Uni Graz
- Desoye Gernot
- Ghaffari Tabrizi-Wizsy Nassim
- Huppertz Berthold
- Lang-Olip Ingrid
- Majali Martinez Alejandro
- Tokic Silvija
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- Abstract:
- The rapidly expanding feto-placental vasculature needs tight control by paracrine and endocrine mechanisms. Here, we focused on paracrine influence by trophoblast, the placental epithelium. We aimed to identify differences in regulation of feto-placental angiogenesis in early versus late pregnancy. To this end, the effect of conditioned media (CM) from early and late pregnancy human trophoblast was tested on network formation, migration and proliferation of human feto-placental endothelial cells. Only CM of late pregnancy trophoblast reduced network formation and migration. Screening of trophoblast transcriptome for anti-angiogenic candidates identified pigment epithelium-derived factor (PEDF) with higher expression and protein secretion in late pregnancy trophoblast. Addition of a PEDF-neutralizing antibody restored the anti-angiogenic effect of CM from late pregnancy trophoblast. Notably, human recombinant PEDF reduced network formation only in combination with VEGF. Also in the CAM assay, the combination of PEDF with VEGF reduced branching of vessels below control levels. Analysis of phosphorylation of ERK1/2 and FAK, two key players in VEGF-induced proliferation and migration, revealed that PEDF altered VEGF signaling, while PEDF alone did not affect phosphorylation of ERK1/2 and FAK. These data suggest that the trophoblast-derived anti-angiogenic molecule PEDF is involved in restricting growth and expansion of the feto-placental endothelium predominantly in late pregnancy and targets to modulate the intracellular effect of VEGF.
- Find related publications in this database (using NLM MeSH Indexing)
- Angiogenesis Inhibitors - physiology
- Animals -
- Antibodies, Neutralizing - administration & dosage
- Cells, Cultured -
- Chick Embryo -
- Culture Media, Conditioned -
- Eye Proteins - antagonists & inhibitors
- Eye Proteins - immunology
- Eye Proteins - physiology
- Female -
- Fetus - blood supply
- Fetus - physiology
- Humans -
- Neovascularization, Physiologic -
- Nerve Growth Factors - antagonists & inhibitors
- Nerve Growth Factors - immunology
- Nerve Growth Factors - physiology
- Paracrine Communication -
- Placenta - blood supply
- Placenta - physiology
- Pregnancy -
- Pregnancy Trimester, First -
- Pregnancy Trimester, Third -
- Serpins - immunology
- Serpins - physiology
- Trophoblasts - physiology
- Vascular Endothelial Growth Factor A - physiology
- Vascular Endothelial Growth Factor Receptor-2 - physiology
- Find related publications in this database (Keywords)
- Trophoblast
- Endothelium
- Angiogenesis
- Placenta
- PEDF
- VEGF