title: TNFα-induced down-regulation of Sox18 in endothelial cells is dependent on NF-κB.
abstract: The transcription factor Sox18 plays a role in angiogenesis, including lymphangiogenesis, where it is upregulated by growth factors and directs the expression of genes encoding, e.g., guidance molecules and a matrix metalloproteinase. Conversely, we found that in human umbilical vein endothelial cells (HUVEC) Sox18 is repressed by the pro-inflammatory mediator TNFα (as well as IL-1 and LPS). Since a common feature of these mediators is the activation of the NF-κB signaling pathway, we investigated whether Sox18 downregulation is dependent on this transcription factor. Transduction of HUVEC with an adenoviral vector directing the expression of the NF-κB inhibitor IκBα prevented the downregulation of Sox18. Transient transfections of Sox18 promoter reporter genes revealed that the downregulation takes place on the level of transcription, and that the p65/RelA subunit of NF-κB was operative. Furthermore, the responsible promoter region of Sox18 is located within -1.0kb from the transcriptional start site. The repression of Sox18 and its target genes may lead to altered formation of vessels in inflamed settings.
authors.affiliation: Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Lazarettg. 19, Vienna, Austria.
authors.forename: José
authors.initials: J
authors.lastname: Basílio
authors.forename: Martina
authors.initials: M
authors.lastname: Hoeth
authors.forename: Yvonne M
authors.initials: YM
authors.lastname: Holper-Schichl
authors.forename: Ulrike
authors.initials: U
authors.lastname: Resch
authors.forename: Herbert
authors.initials: H
authors.lastname: Mayer
authors.forename: Renate
authors.initials: R
authors.lastname: Hofer-Warbinek
authors.forename: Rainer
authors.initials: R
authors.lastname: de Martin
mesh_terms: D015536:Down-Regulation; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics*; D011401:Promoter Regions, Genetic; D055760:SOXF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016328:NF-kappa B; C095473:SOX18 protein, human; D055760:SOXF Transcription Factors; D014409:Tumor Necrosis Factor-alpha
keywords: Endothelial cells; Inflammation; NF-κB; Sox18