Overexpressed fibulin-3 contributes to the pathogenesis of psoriasis by promoting angiogenesis

Background 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. Aim To investigate the role of Fib3 in the pathogenesis of psoriasis. Methods 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. Results 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. Conclusions 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.