A novel angiogenic peptide, ΔADT: A truncated adrenotensin peptide revealed by secretory peptidome analysis of human retinal pericytes.

Abstract

Retinal pericytes play an important role in the maintenance of retinal microvascular homeostasis. We performed a secretory peptidome of primary human retinal pericytes. Using liquid chromatography-tandem mass spectrometry analysis in the culture medium of retinal pericytes, we identified 256 peptides derived from 114 proteins, and identified a novel partial fragment Leu163-His183 (termed ΔADT) of adrenotensin (ADT). To elucidate the role of ΔADT as a soluble mediator of pericyte-endothelial cell interactions, we investigated the bioactivity of ΔADT in human retinal microvascular endothelial cells (HRMVECs). The cell proliferation assay indicated that the proliferation of HRMVECs was promoted by ADT or ΔADT. Moreover, ΔADT had a greater growth promoting effect than ADT in HRMVECs and induced migration and tube formation of HRMVECs. We also observed actin reorganization and that the levels of phosphorylated focal adhesion kinase in ΔADT stimulated HRMVECs. These results showed that ΔADT induces profound actin reorganization and increases the levels of phosphorylated focal adhesion kinase. Collectively, our study showed that ΔADT has an angiogenic activity, and suggested that ΔADT is a novel angiogenic peptide.