title: Vascular endothelial growth factor production is induced by histone deacetylase 1 and suppressed by von Hippel-Lindau protein in HaCaT cells.
abstract: OBJECTIVE
  In hypoxic tumoral tissues, vascular endothelial growth factor (VEGF) expression is positively regulated by histone deacetylase 1 (HDAC1) and negatively regulated by the tumour suppressor protein von Hippel-Lindau (VHL) via transforming growth factor-alpha (HIF-1alpha). It has been reported that VEGF, HDAC1 and LL-37, but not VHL, are over-expressed in psoriatic skin. Although HIF-1alpha is constitutively expressed in normal keratinocytes, it is not known if HDAC1 and VHL can regulate VEGF production in these cells.
  
  
  METHODS
  The participation of HDAC1 and VHL in the regulation of VEGF expression in HDAC-, VHL- and LL-37-transfected HaCaT cells, and in HaCaT cells treated with HDAC1 inhibitors, was studied.
  
  
  RESULTS
  The production of VEGF was increased in HDAC1- and LL-37-transfected HaCaT cells and maintained in VHL-transfected cells under hypoxic conditions; meanwhile, VEGF production decreased in HaCaT cells treated with TSA, in cells transfected with HDAC1-siRNA, in cells co-transfected with HIF-1alpha-siRNA and pHDAC-1 and in VHL-transfected HaCaT cells. The levels of cytoplasmic HIF-1alpha were high in pLL37-transfected cells and low in pVHL- and pHDAC1-transfected cells; however, HIF-1alpha was detected in the nucleus of the HDAC1-transfected cells. The expression of VEGF was high in cells co-transfected with pHDAC1- and pLL-37, and the expression decreased when pVHL was present.
  
  
  CONCLUSIONS
  These data demonstrate that HDAC1, LL-37 and VHL can modulate the production of VEGF via HIF-1alpha in HaCaT cells.
authors.affiliation: Immunology Department of the Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Mexico City, Mexico.
authors.forename: Angélica
authors.initials: A
authors.lastname: Reynoso-Roldán
authors.forename: Maria L
authors.initials: ML
authors.lastname: Roldán
authors.forename: Juan C
authors.initials: JC
authors.lastname: Cancino-Diaz
authors.forename: Sandra
authors.initials: S
authors.lastname: Rodríguez-Martínez
authors.forename: Mario E
authors.initials: ME
authors.lastname: Cancino-Diaz
mesh_terms: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia; D015603:Keratinocytes / Q000166:cytology; D008856:Microscopy, Fluorescence / Q000379:methods; D011565:Psoriasis / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism*
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D042461:Vascular Endothelial Growth Factor A; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; C497446:VHL protein, human