Under-expression of VHL and over-expression of HDAC-1, HIF-1alpha, LL-37, and IAP-2 in affected skin biopsies of patients with psoriasis

Int J Dermatol. 2007 Mar;46(3):239-46. doi: 10.1111/j.1365-4632.2006.02962.x.

Abstract

Background: A feature of psoriasis is the rapid proliferation of keratinocytes, during which apoptosis is blocked and angiogenesis starts. It is known that tumor hypoxic cells produce histone deacetylase-1 (HDAC-1), which up-regulates hypoxia-inducible factor-1alpha (HIF-1alpha) and down-regulates von Hippel-Lindau (VHL) protein by up-regulating vascular endothelial growth factor (VEGF) expression. It has been reported recently that the porcine peptide PR39 (homologous to human LL-37) has angiogenic and antiapoptotic activity. Thus, LL-37, induced by insulin-like growth factor-1 (IGF-1), could help in the production of VEGF. PR39 also induces the expression of inhibitor of apoptosis protein-2 (IAP-2), which blocks apoptosis. The purpose of this work was to analyze whether these genes and their proteins are expressed in psoriatic biopsies.

Methods: Using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) messenger RNA (mRNA) expression and immunohistochemical staining, we studied VHL, IAP-2, and related genes in skin biopsies from psoriatic patients and healthy subjects.

Results: An over-expression of the mRNA for HDAC-1, HIF-1alpha, LL-37, and IGF-1 in psoriatic skin, in comparison with skin from healthy subjects, was found. The antiangiogenic VHL mRNA and protein were under-expressed in psoriatic skin and highly expressed in healthy skin. The antiapoptotic IAP-2 was over-expressed in dermal endothelial cells from psoriatic skin. The pro-apoptotic Bax, Fas, and FasL mRNAs were expressed.

Conclusions: These findings suggest that there could be an association of HDAC-1, HIF-1alpha, LL-37, VHL, and IAP-2 with angiogenic and apoptotic mechanisms in psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antimicrobial Cationic Peptides / analysis
  • Antimicrobial Cationic Peptides / biosynthesis*
  • Biopsy
  • Cathelicidins
  • Gene Expression Regulation
  • Histone Deacetylase 1
  • Histone Deacetylases / analysis
  • Histone Deacetylases / biosynthesis*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / analysis
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis*
  • Inhibitor of Apoptosis Proteins / analysis
  • Inhibitor of Apoptosis Proteins / biosynthesis*
  • Middle Aged
  • Psoriasis / genetics
  • Psoriasis / metabolism*
  • Psoriasis / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Von Hippel-Lindau Tumor Suppressor Protein / analysis
  • Von Hippel-Lindau Tumor Suppressor Protein / biosynthesis*

Substances

  • Antimicrobial Cationic Peptides
  • Cathelicidins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Inhibitor of Apoptosis Proteins
  • ropocamptide
  • Von Hippel-Lindau Tumor Suppressor Protein
  • HDAC1 protein, human
  • Histone Deacetylase 1
  • Histone Deacetylases
  • VHL protein, human