Epidermal autonomous VEGFA/Flt1/Nrp1 functions mediate psoriasis-like disease

Sci Adv. 2020 Jan 8;6(2):eaax5849. doi: 10.1126/sciadv.aax5849. eCollection 2020 Jan.


Psoriasis is a common chronic skin disorder characterized by keratinocyte hyperproliferation with altered differentiation accompanied by inflammation and increased angiogenesis. It remains unclear whether the first events that initiate psoriasis development occur in keratinocytes or inflammatory cells. Here, using different psoriasis mouse models, we showed that conditional deletion of Flt1 or Nrp1 in epidermal cells inhibited psoriasis mediated by Vegfa overexpression or c-Jun/JunB deletion. Administration of anti-Nrp1 antibody reverted the psoriasis phenotype. Using transcriptional and chromatin profiling of epidermal cells following Vegfa overexpression together with Flt1 or Nrp1 deletion, we identified the gene regulatory network regulated by Vegfa/Nrp1/Flt1 during psoriasis development and uncovered a key role of Fosl1 in regulating the chromatin remodeling mediated by Vegfa overexpression in keratinocytes. In conclusion, our study identifies an epidermal autonomous function of Vegfa/Nrp1/Flt1 that mediates psoriatic-like disease and demonstrates the clinical relevance of blocking Vegfa/Nrp1/Flt1 axis in psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Blocking / pharmacology
  • Chromatin Assembly and Disassembly / drug effects
  • Epidermal Cells / drug effects
  • Epidermal Cells / metabolism*
  • Epidermal Cells / pathology
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Mice, Knockout
  • Neuropilin-1 / metabolism*
  • Phenotype
  • Proto-Oncogene Proteins c-fos / metabolism
  • Psoriasis / genetics
  • Psoriasis / metabolism*
  • Psoriasis / pathology*
  • Signal Transduction / drug effects
  • Transcription Factors / metabolism
  • Transcription, Genetic / drug effects
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism*


  • Antibodies, Blocking
  • JunB protein, mouse
  • Proto-Oncogene Proteins c-fos
  • Transcription Factors
  • Vascular Endothelial Growth Factor A
  • fos-related antigen 1
  • Neuropilin-1
  • Flt1 protein, mouse
  • Vascular Endothelial Growth Factor Receptor-1