Topical application of anti-angiogenic peptides based on pigment epithelium-derived factor can improve psoriasis

Received 5 August 2009; received in revised form 17 December 2009; accepted 17 December 2009. published online 12 July 2010.
Corrected Proof

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<850Da) 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.

Abbreviations: PEDF, pigmented epithelium-derived factor, VEGF, vascular endothelial growth factor

Keywords: Angiogenesis, Keratinocyte, Psoriasis, Pigment epithelium-derived factor, Vascular endothelial growth factor

a Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan

b Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan

c Department of Dermatology, Toyama University School of Medicine, Toyama, Japan

d Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA

Corresponding author at: Department of Dermatology, Hokkaido University Graduate School of Medicine, N 15 W 7, Kita-ku, Sapporo 060-8638, Japan. Tel.: +81 11 706 7387; fax: +81 11 706 7820.

1 These authors contributed equally to this paper.

PII: S0923-1811(09)00372-7

doi:10.1016/j.jdermsci.2009.12.010