Open AccessThe Epidermal Growth Factor-like Domain of CD93 Is a Potent Angiogenic Factor
Author(s) -
Yuan Chung Kao,
Shangqing Jiang,
Wen Chi Pan,
Kuan Chieh Wang,
Po Ku Chen,
Hsi Ju Wei,
Wei Sheng Chen,
Bi Ing Chang,
Guey Yueh Shi,
Hua Wu
Publication year - 2012
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0051647
Subject(s) - angiogenesis , matrigel , microbiology and biotechnology , epidermal growth factor , human umbilical vein endothelial cell , biology , vascular endothelial growth factor , growth factor , endothelial stem cell , endothelium , protein kinase b , vascular endothelial growth factor a , signal transduction , cancer research , biochemistry , endocrinology , in vitro , receptor , vegf receptors
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.