title: The transcription factor SOX18 regulates the expression of matrix metalloproteinase 7 and guidance molecules in human endothelial cells.
abstract: BACKGROUND
  Mutations in the transcription factor SOX18 are responsible for specific cardiovascular defects in humans and mice. In order to gain insight into the molecular basis of its action, we identified target genes of SOX18 and analyzed one, MMP7, in detail.
  
  
  RESULTS
  SOX18 was expressed in HUVEC using a recombinant adenoviral vector and the altered gene expression profile was analyzed using microarrays. Expression of several regulated candidate SOX18 target genes was verified by real-time PCR. Knock-down of SOX18 using RNA interference was then used to confirm the effect of the transcription factor on selected genes that included the guidance molecules ephrin B2 and semaphorin 3G. One gene, MMP7, was chosen for further analysis, including detailed promoter studies using reporter gene assays, electrophoretic mobility shift analysis and chromatin-immunoprecipitation, revealing that it responds directly to SOX18. Immunohistochemical analysis demonstrated the co-expression of SOX18 and MMP7 in blood vessels of human skin.
  
  
  CONCLUSIONS
  The identification of MMP7 as a direct SOX18 target gene as well as other potential candidates including guidance molecules provides a molecular basis for the proposed function of this transcription factor in the regulation of vessel formation.
authors.affiliation: Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Hoeth
authors.forename: Heide
authors.initials: H
authors.lastname: Niederleithner
authors.forename: Renate
authors.initials: R
authors.lastname: Hofer-Warbinek
authors.forename: Martin
authors.initials: M
authors.lastname: Bilban
authors.forename: Herbert
authors.initials: H
authors.lastname: Mayer
authors.forename: Ulrike
authors.initials: U
authors.lastname: Resch
authors.forename: Christof
authors.initials: C
authors.lastname: Lemberger
authors.forename: Oswald
authors.initials: O
authors.lastname: Wagner
authors.forename: Erhard
authors.initials: E
authors.lastname: Hofer
authors.forename: Peter
authors.initials: P
authors.lastname: Petzelbauer
authors.forename: Rainer
authors.initials: R
authors.lastname: de Martin
mesh_terms: D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000235:genetics* / Q000378:metabolism; D046228:Microarray Analysis; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D055760:SOXF Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; C095473:SOX18 protein, human; D055760:SOXF Transcription Factors; D014157:Transcription Factors; D020783:Matrix Metalloproteinase 7