EDF-1, A NOVEL GENE-PRODUCT DOWN-REGULATED IN HUMAN ENDOTHELIAL-CELL DIFFERENTIATION

Endothelial cell differentiation is a crucial step in angiogenesis, He re we report the identification of EDF-1, a novel gene product that is down-regulated when endothelial cells are induced to differentiate in vitro. The cDNA encoding EDF-I was isolated by RNA fingerprinting fro m human endothelial cells exposed to human immunodeficiency virus type 1 Tat, a viral protein known to be angiogenic, The deduced amino acid sequence of EDF-1 encodes a basic intracellular protein of 148 amino acids that is homologous to MBF1 (multiprotein-bridging factor 1) of t he silkworm Bombyx mori and to H7, which is implicated in the early de velopmental events of Dictyostelium discoideum, Interestingly, human i mmunodeficiency virus type 1 Tat, which affects endothelial functions, and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate and cultur e on fibrin gels, which promote endothelial differentiation in vitro, all down-regulate EDF-I expression both at the RNA and protein levels. In addition, the inhibition of EDF I translation by an antisense anti -EDF-l construct results in the inhibition of endothelial cell growth and in the transition from a nonpolar cobblestone phenotype to a polar fibroblast-like phenotype, These data suggest that EDF-1 may play a r ole in the regulation of human endothelial cell differentiation.