Heparanase in Psoriasis: Its Role and Mode of Action
Tzahi Neuman, Immanuel Lerner, Eyal Zcharia, Israel Vlodavsky, Michael Elkin. Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Rappaport Faculty of Medicine, Technion, Haifa, Israel
Background: Heparanase is a predominant mammalian enzyme that cleaves heparan sulfate (HS), the key polysaccharide of the ECM and the basement membranes. Alterations in HS content are characteristic for psoriasis. The role and mode of action of Heparanase in Psoriasis remains to be elucidated.
Design: Immunohistochemical staining was used to assess heparanase expression in skin specimens derived from psoriatic patients and healthy individuals. Heparanase-overexpressing transgenic mice were used to verify the role of heparanase in the pathogenesis of psoriasis utilizing a model of cutaneous inflammation induced by TPA. Immunofluorescence and quantitative RT-PCR were used to study in depth the underlying molecular mechanism.
Results: Heparanase is preferentially expressed in human psoriatic lesions.
Heparanase overexpression creates psoriasis-like phenotype in the mouse skin via generation of inflammation-supportive microenvironment, characterized by enhanced macrophages accumulation (Figure 2), NF-κB signaling, induction of STAT 3 and increased vascularization.
Heparanase-dependent macrophage activation represents a relevant mechanism in pathogenesis of psoriasis.
Conclusions: Our results highlight biological significance of heparanase in psoriasis and reveal possible mechanism of heparanase action. This mechanism involves self-sustained inflammatory circle through which keratinocite-derived heparanase facilitates activation of macrophages, which, in turn, preserve chronic inflammatory conditions in the skin and in parallel stimulate further production/activation of the enzyme by the epithelial compartment.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 79, Wednesday Morning