title: The epidermal growth factor-like domain of CD93 is a potent angiogenic factor.
abstract: Human CD93, an epidermal growth factor (EGF)-like domain containing transmembrane protein, is predominantly expressed in the vascular endothelium. Studies have shown that AA4, the homolog of CD93 in mice, may mediate cell migration and angiogenesis in endothelial cells. Soluble CD93 has been detected in the plasma of healthy individuals. However, the role of soluble CD93 in the endothelium remains unclear. Recombinant soluble CD93 proteins with EGF-like domains (rCD93D123, with domains 1, 2, and 3; and rCD93D23, with domains 2 and 3) were generated to determine their functions in angiogenesis. We found that rCD93D23 was more potent than rCD93D123 in stimulating the proliferation and migration of human umbilical vein endothelial cells (HUVECs). Production of matrix-metalloproteinase 2 increased after the HUVECs were treated with rCD93D23. Further, in a tube formation assay, rCD93D23 induced cell differentiation of HUVECs through phosphoinositide 3-kinase/Akt/endothelial nitric oxide synthase and extracellular signal-regulated kinases-1/2 signaling. Moreover, rCD93D23 promoted blood vessel formation in a Matrigel-plug assay and an oxygen-induced retinopathy model in vivo. Our findings suggest that the soluble EGF-like domain containing CD93 protein is a novel angiogenic factor acting on the endothelium.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yuan-Chung
authors.initials: YC
authors.lastname: Kao
authors.forename: Shinn-Jong
authors.initials: SJ
authors.lastname: Jiang
authors.forename: Wen-An
authors.initials: WA
authors.lastname: Pan
authors.forename: Kuan-Chieh
authors.initials: KC
authors.lastname: Wang
authors.forename: Po-Ku
authors.initials: PK
authors.lastname: Chen
authors.forename: Hsi-Ju
authors.initials: HJ
authors.lastname: Wei
authors.forename: Wei-Sheng
authors.initials: WS
authors.lastname: Chen
authors.forename: Bi-Ing
authors.initials: BI
authors.lastname: Chang
authors.forename: Guey-Yueh
authors.initials: GY
authors.lastname: Shi
authors.forename: Hua-Lin
authors.initials: HL
authors.lastname: Wu
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007797:Laminin / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D009389:Neovascularization, Pathologic; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000737:chemistry; D011951:Receptors, Complement / Q000096:biosynthesis* / Q000235:genetics*; D012162:Retinal Degeneration / Q000473:pathology; D015398:Signal Transduction
chemical_list: D004338:Drug Combinations; D007797:Laminin; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D011951:Receptors, Complement; C032402:complement 1q receptor; C059485:matrigel; D004815:Epidermal Growth Factor; D003094:Collagen; D010100:Oxygen