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Coexistence of Eph receptor B1 and ephrin B2 in port‐wine stain endothelial progenitor cells contributes to clinicopathological vasculature dilatation
Author(s) -
Tan W.,
Wang J.,
Zhou F.,
Gao L.,
Yin R.,
Liu H.,
Sukanthanag A.,
Wang G.,
Mihm M.C.,
Chen D.B.,
Nelson J.S.
Publication year - 2017
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.15716
Subject(s) - port wine stain , erythropoietin producing hepatocellular (eph) receptor , ephrin , progenitor cell , stain , pathology , progenitor , medicine , receptor , anatomy , staining , microbiology and biotechnology , biology , stem cell , receptor tyrosine kinase , laser , physics , optics
Summary Background Port‐wine stain ( PWS ) is a vascular malformation characterized by progressive dilatation of postcapillary venules, but the molecular pathogenesis remains obscure. Objectives To illustrate that PWS endothelial cells ( EC s) present a unique molecular phenotype that leads to pathoanatomical PWS vasculatures. Methods Immunohistochemistry and transmission electron microscopy were used to characterize the ultrastructure and molecular phenotypes of PWS blood vessels. Primary culture of human dermal microvascular endothelial cells and in vitro tube formation assay were used for confirmative functional studies. Results Multiple clinicopathological features of PWS blood vessels during the development and progression of the disease were shown. There were no normal arterioles and venules observed phenotypically and morphologically in PWS skin; arterioles and venules both showed differentiation impairments, resulting in a reduction of arteriole‐like vasculatures and defects in capillary loop formation in PWS lesions. PWS EC s showed stemness properties with expression of endothelial progenitor cell markers CD 133 and CD 166 in non‐nodular lesions. They also expressed dual venous/arterial identities, Eph receptor B1 (EphB1) and ephrin B2 (EfnB2). Co‐expression of EphB1 and EfnB2 in normal human dermal microvascular EC s led to the formation of PWS ‐like vasculatures in vitro , for example larger‐diameter and thick‐walled capillaries. Conclusions PWS EC s are differentiation‐impaired, late‐stage endothelial progenitor cells with a specific phenotype of CD 133 + / CD 166 + /EphB1 + /EfnB2 + , which form immature venule‐like pathoanatomical vasculatures. The disruption of normal EC – EC interactions by coexistence of EphB1 and EfnB2 contributes to progressive dilatation of PWS vasculatures.