Resistin promotes angiogenesis in endothelial progenitor cells through inhibition of microRNA‐206

Abstract

Resistin has a proinflammatory function in human that contributes to the link between inflammation and cardiovascular disease and is also associated with rheumatoid arthritis (RA).The aim of this study was to examine the potential function ofresistin in human circulating endothelial progenitor cells (EPCs) during angiogenesis in RA.EPCs isolated from healthy donors were used to investigate the mechanisms underlying EPCs migration and tube formation. In addition, potential microRNA‐206 (miR‐206) targets were validated using real‐time quantitative polymerase chain reaction, western blotting, and a luciferase reporter assay. Resistin is highly expressed in synovial fluids and tissues in RA patients and mice with collagen‐induced arthritis and promotes both EPC homing to synovia and angiogenesis. We show that resistin directly induces significant upregulation of vascular endothelial growth factor (VEGF) expression in EPCs and promotes expression of the VEGF 3ʹ untranslated region in the absence of a miR‐206 binding site. Our study is the first to demonstrate that a signaling pathway involving miR‐206 is involved in resistin‐induced VEGF expression and that EPCs migrate into RA joints in vitro and in vivo; these results provide support for resistin as a therapeutic target of RA.