Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
J Dermatol Sci. 2010 Mar;57(3):183-91. doi: 10.1016/j.jdermsci.2009.12.010. Epub 2010 Jan 8.
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.
We investigated to identify small peptide mimetics of PEDF that might show anti-angiogenic potential for the topical treatment for psoriasis.
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.
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.
These data suggest that low-molecular PEDF peptides with anti-angiogenic activity may be a novel therapeutic strategy for psoriasis.
银屑病是一种常见的慢性炎症性皮肤疾病,在白种人群中的患病率为 3-5%。尽管银屑病皮损中的毛细血管数量增加,但很少有研究专门探讨血管生成在银屑病中的作用。血管生成因子,如血管内皮生长因子(VEGF),可能会主导抗血管生成因子的活性,并加速银屑病皮肤中的血管生成。
我们旨在寻找 PEDF 的小分子肽模拟物,这些模拟物可能具有抗血管生成的潜力,可用于治疗银屑病的局部治疗。
我们通过免疫组织化学染色、免疫印迹和 RT-PCR 来检测 PEDF 在皮肤中的表达。为了鉴定潜在的 PEDF 肽,我们筛选了 PEDF 蛋白水解片段中的肽,以研究其抗增殖作用。使用银屑病小鼠移植模型分析这些肽的抗银屑病功能。
这些特定的低分子量肽(MW<850 Da)能够穿透皮肤,在体外表现出显著的抗血管生成活性。在严重联合免疫缺陷小鼠银屑病模型中局部应用这些肽可减少血管生成和表皮厚度。
这些数据表明,具有抗血管生成活性的低分子量 PEDF 肽可能是治疗银屑病的一种新的治疗策略。