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http://purl.uniprot.org/citations/15665520http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15665520http://www.w3.org/2000/01/rdf-schema#comment"Renal proximal tubular epithelial cells (PTEC) respond to hypoxia exposure or interleukin-1beta (IL-1beta) treatment with increased vascular endothelial growth factor (VEGF) production. With respect to O2 deprivation, the hypoxia-inducible factor 1alpha/ beta (HIF-1) is the most important transcription factor driving VEGF mRNA expression. HIF-1 is also activated by IL-1beta and may thus be involved in the stimulation of VEGF production by this cytokine. However, the molecular mechanisms of HIF-1 dependent VEGF synthesis are poorly understood. Herein, human PTEC in primary culture were challenged by hypoxic incubation and/or IL-1beta treatment in absence or presence of specific phosphatidylinositol 3-kinase (PI3K) or mitogen activated protein kinase kinase-1 (MAPKK-1) inhibitors for assay of VEGF protein, VEGF mRNA and detection of HIF-1alpha by Western Blotting, EMSA and fluorescence microscopy. In addition, the activities of PI3K and MAPKK-1 were studied following hypoxia and IL-1beta treatment of the cultures. The study shows that PI3K but not MAPKK-1 inhibition resulted in the loss of hypoxic and IL-1beta induced HIF-1alpha accumulation, whereas VEGF synthesis was reduced by either intervention. Thus, PI3K signaling is required for HIF-1alpha accumulation and VEGF synthesis, whereas MAPKK-1 signaling is required for VEGF synthesis only. Furthermore, hypoxia alone was sufficient to activate PI3K in PTEC in contrast to MAPKK-1, whose activity was lowered in hypoxia."xsd:string
http://purl.uniprot.org/citations/15665520http://purl.org/dc/terms/identifier"doi:10.1159/000083642"xsd:string
http://purl.uniprot.org/citations/15665520http://purl.uniprot.org/core/author"Jelkmann W."xsd:string
http://purl.uniprot.org/citations/15665520http://purl.uniprot.org/core/author"Katschinski D.M."xsd:string
http://purl.uniprot.org/citations/15665520http://purl.uniprot.org/core/author"Stiehl D.P."xsd:string
http://purl.uniprot.org/citations/15665520http://purl.uniprot.org/core/author"Kreft B."xsd:string
http://purl.uniprot.org/citations/15665520http://purl.uniprot.org/core/author"Hellwig-Burgel T."xsd:string
http://purl.uniprot.org/citations/15665520http://purl.uniprot.org/core/author"Marxsen J."xsd:string
http://purl.uniprot.org/citations/15665520http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/15665520http://purl.uniprot.org/core/name"Cell Physiol Biochem"xsd:string
http://purl.uniprot.org/citations/15665520http://purl.uniprot.org/core/pages"99-108"xsd:string
http://purl.uniprot.org/citations/15665520http://purl.uniprot.org/core/title"VEGF production by primary human renal proximal tubular cells: requirement of HIF-1, PI3-kinase and MAPKK-1 signaling."xsd:string
http://purl.uniprot.org/citations/15665520http://purl.uniprot.org/core/volume"15"xsd:string
http://purl.uniprot.org/citations/15665520http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/15665520
http://purl.uniprot.org/citations/15665520http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/15665520
http://purl.uniprot.org/uniprot/#_D0VY79-mappedCitation-15665520http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15665520
http://purl.uniprot.org/uniprot/#_B4DFY5-mappedCitation-15665520http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15665520
http://purl.uniprot.org/uniprot/#_B2R617-mappedCitation-15665520http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15665520
http://purl.uniprot.org/uniprot/#_A4QPA9-mappedCitation-15665520http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15665520
http://purl.uniprot.org/uniprot/#_A8MYV6-mappedCitation-15665520http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15665520
http://purl.uniprot.org/uniprot/#_B4E2K5-mappedCitation-15665520http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15665520
http://purl.uniprot.org/uniprot/#_B4E2U7-mappedCitation-15665520http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15665520
http://purl.uniprot.org/uniprot/#_B4DL76-mappedCitation-15665520http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15665520
http://purl.uniprot.org/uniprot/#_B4DS34-mappedCitation-15665520http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15665520