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http://purl.uniprot.org/citations/24260556http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24260556http://www.w3.org/2000/01/rdf-schema#comment"Vascular endothelial growth factor receptor 2 (VEGFR-2), the primary receptor for VEGF, is crucial for normal endothelial function. sFlt-1, a truncated and soluble form of VEGFR-1 which binds and inhibits VEGF, is increased in preeclampsia and is positively regulated by low oxygen. Here, we investigated the effects of sFlt-1 and hypoxia on VEGFR-2 expression and signaling in the human placenta. VEGFR-2 transcript and protein levels were significantly decreased in preeclamptic placentae compared to controls (1.82 and 1.85 fold, respectively). An inverse correlation was observed for VEGFR-2 and sFlt-1 levels in both singleton and twin placentae from patients with preeclampsia. Immunofluorescence analyses revealed co-localization of VEGFR-2 and sFlt-1 in placental vasculature and co-immunoprecipitation analyses confirmed VEGFR-2 and sFlt-1 interaction only in preeclamptic placentae compared to age-matched controls. VEGFR-2 transcript and protein levels from explants cultured in 3% O2 were significantly decreased compared to those incubated at 20% O2 (5.9 and 12.47 fold, respectively). Also, VEGFR-2 transcript levels were significantly decreased in early first trimester placentae (low oxygen environment) compared to late first trimester placentae (2.05 fold). We next explored whether sFlt-1 directly affects VEGFR-2 expression. Treatment of first trimester placental explants with sFlt-1 resulted in significantly decreased levels of VEGFR-2 (2.03 fold) and downstream signaling proteins phospho-ERK (1.60 fold) and phospho-Akt (1.64 fold). Our findings show a novel hypoxia-induced and PE-related down-regulation of VEGFR-2 in the human placenta. sFlt-1, which is known to be increased in hypoxic conditions and PE, directly attenuates VEGFR-2 expression and signaling. A direct interaction between sFlt-1 and VEGFR-2 may represent an important mechanism in VEGFR-2 regulation, inhibition of VEGFR-2-mediated processes in placentation and a novel platform to examine the onset of preeclampsia."xsd:string
http://purl.uniprot.org/citations/24260556http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0081176"xsd:string
http://purl.uniprot.org/citations/24260556http://purl.uniprot.org/core/author"Caniggia I."xsd:string
http://purl.uniprot.org/citations/24260556http://purl.uniprot.org/core/author"Lee D.K."xsd:string
http://purl.uniprot.org/citations/24260556http://purl.uniprot.org/core/author"Nevo O."xsd:string
http://purl.uniprot.org/citations/24260556http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/24260556http://purl.uniprot.org/core/name"PLoS One"xsd:string
http://purl.uniprot.org/citations/24260556http://purl.uniprot.org/core/pages"e81176"xsd:string
http://purl.uniprot.org/citations/24260556http://purl.uniprot.org/core/title"Attenuation of VEGFR-2 expression by sFlt-1 and low oxygen in human placenta."xsd:string
http://purl.uniprot.org/citations/24260556http://purl.uniprot.org/core/volume"8"xsd:string
http://purl.uniprot.org/citations/24260556http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/24260556
http://purl.uniprot.org/citations/24260556http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/24260556
http://purl.uniprot.org/uniprot/#_A0A0U2WZU8-mappedCitation-24260556http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24260556
http://purl.uniprot.org/uniprot/#_A0A0U2X4C8-mappedCitation-24260556http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24260556
http://purl.uniprot.org/uniprot/#_A0A0H4A777-mappedCitation-24260556http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24260556
http://purl.uniprot.org/uniprot/#_A0A0H4A7S0-mappedCitation-24260556http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24260556
http://purl.uniprot.org/uniprot/#_A0A0H4A7S4-mappedCitation-24260556http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24260556
http://purl.uniprot.org/uniprot/#_A0A0H4ADZ1-mappedCitation-24260556http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24260556
http://purl.uniprot.org/uniprot/#_A0A0H4AF76-mappedCitation-24260556http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24260556
http://purl.uniprot.org/uniprot/#_A0A0H4AF85-mappedCitation-24260556http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24260556
http://purl.uniprot.org/uniprot/#_A0A0U2VU55-mappedCitation-24260556http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24260556
http://purl.uniprot.org/uniprot/#_H9N1E7-mappedCitation-24260556http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24260556
http://purl.uniprot.org/uniprot/#_H9N1E8-mappedCitation-24260556http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24260556
http://purl.uniprot.org/uniprot/#_B5A924-mappedCitation-24260556http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24260556