Insulin-like Growth Factor-II (IGF-II) Induces Vascular Endothelial Growth Factor (VEGF) Expression through IGFR-1 and ERK1/2 Activation in Psoriasis / 대한피부과학회지

ABSTRACT

BACKGROUND: Psoriasis is a chronic relapsing and angiogenic skin disease characterized by variable clinical features. But the pathogenetic process resulting in vascular morphological changes remains to be proven. It is reported that the potent angiogenic factor VEGF is overexpressed in psoriatic epidermis and the level of IGF-II is significantly elevated in tissue fluid and serum of the psoriatic lesion. OBJECTIVE AND METHOD: To find the mechanism of VEGF induction in pathogenesis of psoriasis, we adopt IGF-II as a paracrine inducer of VEGF in psoriasis. To investigate the signaling pathway of IGF-II-induced VEGF, we determined ERK1/2 activity in IGF-II-treated psoriatic cells. RESULT: In this report, we demonstrated that IGF-II induced the expression of VEGF in lesional keratinocytes of psoriasis. And IGF-II stimulated the expression of its receptor, IGFR-I in psoriatic cells. Treatment of anti-IGFR-I neutralizing antibody diminished VEGF mRNA level induced by IGF-II, indicating that VEGF induction by IGF-II may be mediated through IGFR-I. By the treatment of PD98059, specific inhibitor of upstream ERK activator MAP kinase/ERK kinase (MEK), the expression of VEGF induced by IGF-II was dramatically reduced. CONCLUSION: Taken together, these results suggest that IGF-II might regulate angiogenesis by the induction of VEGF through the MAP kinase pathway mediated by IGFR-I in the lesion of psoriasis.