Aminopeptidase N/CD13 induces angiogenesis through interaction with a pro-angiogenic protein, galectin-3.

Aminopeptidase N/CD13 is an endothelial cell surface ectoenzyme involved in one of the initial steps of angiogenesis. However, little is known how APN induces angiogenesis in endothelial cells. Using human cDNA library-encoding phage display biopanning method, we here identified a galactoside-specific lectin family protein, galectin-3, as an interacting protein of APN. Galectin-3 specifically binds to APN both in vitro and in human umbilical vein endothelial cells (HUVECs) in a carbohydrate recognition-dependent manner. Immunohistochemical analysis demonstrates that both APN and galectin-3 are exclusively coexpressed during the angiogenic stage of mouse forebrain development. Finally, exogenous addition of galectin-3 into HUVECs induced angiogenesis in an APN-dependent manner, implying that APN is a crucial mediator of galectin-3-induced angiogenesis in endothelial cells.