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Titolo: New insights into the machanism of PPAR gamma regulation of trophoblast invasion and placental vascularization.
Data di pubblicazione: 2014
Abstract: Objectives: PPARγ-deficient mice develop severe placental abnormalities with defects in trophoblast invasion and placental vascularisation. However, the mechanism by which this occurs is still unknown. We have recently shown that the new angiogenic factor EG-VEGF (Endocrine gland-derived vascular endothelial growth factor) controls the same processes of placental development as PPARγ. Moreover, in silico analysis of EG-VEGF promoter showed potential response elements for PPARγ, suggesting a potential regulation of EG-VEGF by PPARγ. EG-VEGF exerts its functions via prokineticin receptor 1 (PROKR1) and 2 (PROKR2). We hypothesized that PPARγ effects on trophoblast invasion and placental vascularization might, in part, be mediated by EG-VEGF signalling. Methods: Both in vitro and in vivo studies were used. In vitro studies used human placental explants (8–10 wg), Primary cytotrophoblasts and HTR-8/SVneo. PPARγ agonist (Rosiglitazone) was tested on i) EG-VEGF and its receptors expression ii) EG-VEGF secretion, iii) trophoblast, proliferation, migration and invasion iv) placental vascularisation, in the absence or presence of PROKR1 and PROKR2 antagonists. In vivo studies used PPARγ deficient mice in which placental levels of EG-VEGF and its receptors were assessed. Results: We demonstrated that 1) rosiglitazone induced EG-VEGF secretion and expression, from 8 hours of treatment and increased PROKR2, but not PROKR1 expression, 2) PPARγ antagonist (T0070907) decreased EG-VEGF secretion, 3) EG-VEGF don’t regulate PPARγ expression, 4) PPARγ control of placental vascularisation is mediated by PROKR1 and PROKR2, and 5) PPARγ inhibition of trophoblast invasion is in part mediated by PROKR2 but not PROKR1. In vivo analysis did not show any difference in placental EG-VEGF, PROKR1 and PROKR2 levels. Conclusion: Altogether these data demonstrate a direct regulation of EG-VEGF and its receptor PROKR2 by the nuclear receptor PPARγ, and bring new insights into the mechanism by which PPARγ regulates trophoblast invasion and vascularisation.
Tipologia:4.2 Abstract in Atti di convegno

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