916
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
1
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
#
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 .