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INVESTIGATIVE REPORT ActaDV ActaDV Advances in dermatology and venereology Acta Dermato-Venereologica
Psoriasis and Pro-angiogenetic Factor CD93: Gene Expression and Association with Gene Polymorphism Suggests a Role in Disease Pathogenesis
Albert DUVETORP 1 #, Renate SLIND OLSEN 2, 3 #, Marita SKARSTEDT 3, Jan SÖDERMAN 3 and Oliver SEIFERT 1, 4
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Division of Dermatology and Venereology, 3 Department of Laboratory Medicine, Division of Medical Diagnostics, Region Jönköping County, Jönköping, 2 Division of Drug Research, Department of Medicine and Health Sciences, and 4 Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden
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These authors contributed equally to this work.
CD93 is involved in angiogenesis and inflammation, both of which are key processes in the pathogenesis of psoriasis. CD93 was studied in serum, peripheral blood mononuclear cells and skin of patients with psoriasis and controls. Furthermore, allele frequencies for CD93 single-nucleotide polymorphisms rs2749812 and rs2749817 were assessed in patients with psoriasis compared with controls and the effect of narrowband ultraviolet B( NB-UVB) treatment on CD93 gene expression was evaluated in the skin of patients with psoriasis. CD93 gene expression was significantly increased in lesional and non-lesional skin from patients with psoriasis compared with controls. Immunohistochemistry revealed CD93 staining in dermal endothelial cells in lesional skin, and psoriasis was significantly associated with rs2749817 CD93 gene polymorphism. NB-UVB treatment of patients with psoriasis did not alter skin CD93 gene expression. Increased protein expression of CD93 psoriatic skin and association with the rs2749817 polymorphism suggests that CD93 plays a role in psoriasis disease pathogenesis.
Key words: psoriasis; CD93; angiogenesis; single nucleotide polymorphism; ultraviolet B; phototherapy.
Accepted Apr 18, 2017; Epub ahead of print Apr 19, 2017 Acta Derm Venereol 2017; 97: 916 – 921.
Corr: Albert Duvetorp, Division of Dermatology, Ryhov Hospital, SE- 55185 Jönköping, Sweden. E-mail: albert. duvetorp @ rjl. se
Psoriasis is a chronic inflammatory skin disease characterized by activated innate immunity, altered differentiation and hyperproliferation of keratinocytes and angiogenesis( 1). In lesional skin of patients with psoriasis, dermal papillae are elongated and dilated blood vessels are present. In fact, angiogenesis and vascular changes are early signs in psoriasis, being detectable even before visible epidermal hyperplasia( 2).
High levels of pro-angiogenic factors, such as vascular endothelial growth factor( VEGF), interleukin 17( IL- 17), interferon( IFN)-γ, tumour necrosis factor( TNF)-α, angiopoietins and hypoxia inducible factor( HIF), are present in lesional skin( 2), and it is suggested that many of the current systemic therapies for psoriasis are not solely immune modifiers, but also inhibit angiogenesis. Recent case reports have shown that vascular endothelial growth factor( VEGF)-inhibitors used in anti-tumour therapy can improve the clinical appearance of psoriasis( 3, 4). Targeting angiogenesis may be a new future treatment strategy for psoriasis( 5).
Recent studies suggest that CD93 may have implications in inflammation and inflammatory diseases as well as in angiogenesis( 6). CD93 is a transmembrane glycoprotein that, together with human endosialin and thrombomodulin, constitutes a small family of transmembrane proteins with epidermal growth factor( EGF)-like domains( 7, 8). CD93 is mainly expressed in endothelial cells, but is also present in granulocytes, monocytes, platelets and stem cells( 9 – 13). The EGF-like domains of CD93 induces endothelial cell proliferation and migration in vitro and stimulates angiogenesis in vivo( 14). 4E1, a monoclonal antibody against CD93 has been shown to inhibit angiogenesis, both in vitro and in vivo, without affecting endothelial cell survival( 15). Previous studies suggest that the expression of CD93 on endothelial cells may also play a role in the regulation of cell adhesion and in the skin homing of inflammatory cells( 10, 16, 17), which are important steps in initiating and maintaining inflammation in psoriasis( 18).
At present, there are no studies on CD93 in psoriasis. The aim of this study is to analyse CD93 expression in non-lesional and lesional skin, in peripheral blood mononuclear cells( PBMCs) and serum of patients with chronic plaque-type psoriasis compared with healthy controls. Two CD93 single-nucleotide polymorphisms( SNPs; rs2749812 and rs2749817) previously associated with increased risk for cardiovascular disease and cancer development( 19, 20) were analysed for a genetic association with psoriasis.
Narrowband UVB( NB-UVB) is a well-tolerated and effective treatment for psoriasis. The anti-inflammatory effect of NB-UVB is partly explained by increased T-cell apoptosis, reduced epidermal proliferation and inhibition of angiogenesis( 21 – 29). To investigate a possible role of CD93 in the anti-inflammatory effect of NB-UVB CD93 gene expression was analysed in psoriasis patients before and after receiving a full standard NB-UVB regime. doi: 10.2340 / 00015555-2682 Acta Derm Venereol 2017; 97: 916 – 921
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2017 Acta Dermato-Venereologica.