Topical application of anti-angiogenic peptides based on pigment epithelium-derived factor can improve psoriasis.
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.
Abe
Riichiro
R
Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. aberi@med.hokudai.ac.jp
Yamagishi
Sho-ichi
S
Fujita
Yasuyuki
Y
Hoshina
Daichi
D
Sasaki
Mikako
M
Nakamura
Kazuo
K
Matsui
Takanori
T
Shimizu
Tadamichi
T
Bucala
Richard
R
Shimizu
Hiroshi
H
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
D020533:Angiogenesis Inhibitors; D005136:Eye Proteins; D008070:Lipopolysaccharides; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor