title: Topical application of anti-angiogenic peptides based on pigment epithelium-derived factor can improve psoriasis.
abstract: BACKGROUND
  Psoriasis is a common chronic inflammatory skin disorder with a high prevalence (3-5%) in the Caucasian population. Although the number of capillary vessels increases in psoriatic lesions, there have been few reports that have specifically examined the role of angiogenesis in psoriasis. Angiogenic factors, such as vascular endothelial growth factor (VEGF), may dominate the activity of anti-angiogenic factors and accelerate angiogenesis in psoriatic skin.
  
  
  OBJECTIVE
  We investigated to identify small peptide mimetics of PEDF that might show anti-angiogenic potential for the topical treatment for psoriasis.
  
  
  METHODS
  We examined the expression of PEDF in skin by immunohistochemical staining, immunoblotting, and RT-PCR. To identify potential PEDF peptides, we screened peptides derived from the proteolytic fragmentation of PEDF for their anti-proliferative action. Anti-psoriatic functions of these peptides were analyzed using a mouse graft model of psoriasis.
  
  
  RESULTS
  The specific low-molecular weight peptides (MW<850 Da) penetrated the skin and showed significant anti-angiogenic activity in vitro. Topical application of these peptides in a severe combined immunodeficient mouse model of psoriatic disease led to reduced angiogenesis and epidermal thickness.
  
  
  CONCLUSIONS
  These data suggest that low-molecular PEDF peptides with anti-angiogenic activity may be a novel therapeutic strategy for psoriasis.
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. aberi@med.hokudai.ac.jp
authors.forename: Riichiro
authors.initials: R
authors.lastname: Abe
authors.forename: Sho-ichi
authors.initials: S
authors.lastname: Yamagishi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujita
authors.forename: Daichi
authors.initials: D
authors.lastname: Hoshina
authors.forename: Mikako
authors.initials: M
authors.lastname: Sasaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakamura
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsui
authors.forename: Tadamichi
authors.initials: T
authors.lastname: Shimizu
authors.forename: Richard
authors.initials: R
authors.lastname: Bucala
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects*; D005136:Eye Proteins / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015552:Injections, Intralesional; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism; D015843:Serpins / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D020533:Angiogenesis Inhibitors; D005136:Eye Proteins; D008070:Lipopolysaccharides; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor