Expression of the vanin gene family in normal and inflamed human skin: induction by proinflammatory cytokines

J Invest Dermatol. 2009 Sep;129(9):2167-74. doi: 10.1038/jid.2009.67. Epub 2009 Mar 26.


The vanin gene family encodes secreted and membrane-bound ectoenzymes that convert pantetheine into pantothenic acid and cysteamine. Recent studies in a mouse colitis model indicated that vanin-1 has proinflammatory activity and suggest that pantetheinases are potential therapeutic targets in inflammatory diseases. In a microarray analysis of epidermal gene expression of psoriasis and atopic dermatitis lesions, we identified vanin-3 as the gene showing the highest differential expression of all annotated genes that we studied (19-fold upregulation in psoriasis). Quantitative real-time PCR analysis confirmed the microarray data on vanin-3 and showed similar induction of vanin-1, but not of vanin-2, in psoriatic epidermis. Immunohistochemistry showed that vanin-3 is expressed in the differentiated epidermal layers. Using submerged and organotypic keratinocyte cultures, we found that vanin-1 and vanin-3 are induced at the mRNA and protein level by psoriasis-associated proinflammatory cytokines (Th17/Th1) but not by Th2 cytokines. We hypothesize that increased levels of pantetheinase activity are part of the inflammatory-regenerative epidermal differentiation program, and may contribute to the phenotype observed in psoriasis.

MeSH terms

  • Amidohydrolases / genetics*
  • Caspase Inhibitors
  • Cell Adhesion Molecules / analysis
  • Cell Adhesion Molecules / genetics*
  • Cysteamine / pharmacology
  • Cytokines / pharmacology*
  • GPI-Linked Proteins
  • Gene Expression Regulation / drug effects
  • Humans
  • Hydrolases / analysis
  • Hydrolases / genetics*
  • Keratinocytes / metabolism
  • PPAR gamma / physiology
  • Psoriasis / metabolism*
  • RNA, Messenger / analysis
  • Skin / metabolism
  • Transglutaminases / antagonists & inhibitors


  • Caspase Inhibitors
  • Cell Adhesion Molecules
  • Cytokines
  • GPI-Linked Proteins
  • PPAR gamma
  • RNA, Messenger
  • Cysteamine
  • Transglutaminases
  • Hydrolases
  • Amidohydrolases
  • pantetheinase
  • VNN2 protein, human
  • VNN3 protein, human