Department of Dermatology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Dermatology, Shaanxi Provincial People's Hospital, Xi'an, China.
Clin Exp Dermatol. 2019 Jun;44(4):e64-e72. doi: 10.1111/ced.13720. Epub 2018 Aug 26.
Psoriasis is a chronic inflammatory skin disease. The earliest and most significant pathological change in psoriasis is angiogenesis. Fibulin-3 (Fib3) (also known as epidermal growth factor-containing fibulin-like extracellular matrix protein 1; EFEMP1) is a widely expressed extracellular matrix glycoprotein, which plays an important but contradictory role in regulating angiogenesis. However, the contribution of Fib3 to psoriasis remains unknown.
To investigate the role of Fib3 in the pathogenesis of psoriasis.
We first examined Fib3 expression in psoriasis cells and patient samples. We then investigated the relationship between Fib3 and angiogenesis by coculturing keratinocytes with vascular endothelial cells. Finally, we tested the therapeutic effect of a Fib3 antibody in a mouse model of psoriasis.
Fib3 was overexpressed in the lesional skin of patients with psoriasis, and Fib3 levels positively correlated with psoriasis progression. Using a keratinocyte and endothelial cell coculture system, we found that keratinocyte-derived Fib3 upregulated vascular endothelial growth factor (VEGF) expression in endothelial cells and induced endothelial cell proliferation and migration. Topical application or subcutaneous injection of the Fib3 antibody decreased Psoriasis Area and Severity Index and VEGF expression in imiquimod-treated mice.
Taken together, these results suggest that Fib3 is involved in the pathogenesis of psoriasis by promoting angiogenesis. Fib3 could serve as a potential target for treating psoriasis.
银屑病是一种慢性炎症性皮肤病。银屑病最早和最显著的病理变化是血管生成。纤连蛋白-3（Fib3）（也称为含有表皮生长因子的纤连蛋白样细胞外基质蛋白 1；EFEMP1）是一种广泛表达的细胞外基质糖蛋白，在调节血管生成方面发挥着重要但矛盾的作用。然而，Fib3 对银屑病的贡献尚不清楚。
研究 Fib3 在银屑病发病机制中的作用。
我们首先检查了银屑病细胞和患者样本中的 Fib3 表达。然后，我们通过角质形成细胞与血管内皮细胞共培养来研究 Fib3 与血管生成之间的关系。最后，我们在银屑病小鼠模型中测试了 Fib3 抗体的治疗效果。
Fib3 在银屑病患者的皮损皮肤中过度表达，并且 Fib3 水平与银屑病的进展呈正相关。使用角质形成细胞和内皮细胞共培养系统，我们发现角质形成细胞衍生的 Fib3 上调了内皮细胞中血管内皮生长因子（VEGF）的表达，并诱导了内皮细胞的增殖和迁移。在咪喹莫特处理的小鼠中，局部应用或皮下注射 Fib3 抗体可降低银屑病面积和严重程度指数以及 VEGF 的表达。
综上所述，这些结果表明 Fib3 通过促进血管生成参与银屑病的发病机制。Fib3 可以作为治疗银屑病的潜在靶点。
