Deleted in Malignant Brain Tumors 1 is Present in the Vascular Extracellular Matrix and Promotes Angiogenesis

• DOI: 10.1161/atvbaha.111.239830
• Publication Date: 2011-11-04T04:48:19Z
• Authors: Hanna Müller; Jiong Hu; Rüdiger Popp; Mirko H.H. Schmidt; Karin Müller-Decker; Jan Mollenhauer; Beate Fisslthaler; Johannes A. Eble; Ingrid Fleming
• Keywords: Male; Mice, Knockout; 0303 health sciences; Receptors, Notch; Galectin 3; Tumor Suppressor Proteins; Calcium-Binding Proteins; Medizin; Mucins; Neovascularization, Physiologic; Extracellular Matrix; DNA-Binding Proteins; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Cell Movement; Models, Animal; Cell Adhesion; Animals; Endothelium, Vascular; Cells, Cultured; Signal Transduction

Deleted in malignant brain tumors 1 (DMBT1) belongs to the scavenger receptor cysteine-rich superfamily of proteins and is implicated innate immunity, cell polarity, differentiation. Here we studied role DMBT1 endothelial cells.DMBT1 was secreted into extracellular matrix (ECM) by cells vitro situ presence ECM increased adherence. Endothelial cell-derived associated with galectin-3 (coprecipitation), human recombinant bound EGF, vascular growth factor Delta-like (Dll) 4 (specific ELISAs). Compared from wild-type mice, DMBT1(-/-) mice demonstrated reduced migration, proliferation, tube formation. In vivo recovery hindlimb ischemia attenuated animals as -induced sprouting isolated aortic rings; latter response could be rescued addition DMBT1. The Notch pathway involved multiple aspects development, including arterial-venous differentiation found that expressed more EphrinB2 than mice. Levels Dll1, Dll4, Hes1, Hey1, EphB4, on other hand, were decreased.Taken together, results this study indicate functions an important endothelium-derived protein able bind angiogenic factors promote adhesion, angiogenesis well repair. Mechanistically, interacts modulates signaling differential expression ephrin-B2 EphB4.