Coactivation of Tie2 and Wnt signaling using an antibody-R-spondin fusion potentiates therapeutic angiogenesis and vessel stabilization in hindlimb ischemia.

ABSTRACT: Therapeutic angiogenesis by intentional formation of blood vessels is essential for treating various ischemic diseases, including limb ischemia. Because Wnt/β-catenin and angiopoietin-1/Tie2 signaling play important roles in endothelial survival and vascular stability, coactivation of these signaling pathways can potentially achieve therapeutic angiogenesis. In this study, we developed a bifunctional antibody fusion, consisting of a Tie2-agonistic antibody and the Furin domains of R-spondin 3 (RSPO3), to simultaneously activate Tie2 and Wnt/β-catenin signaling. We identified a Tie2-agonistic antibody T11 that cross-reacted with the extracellular domain of human and mouse Tie2, and evaluated its ability to increase endothelial cell survival and tube formation. We generated a bifunctional T1

SUBMITTER: Hwang B 

PROVIDER: S-EPMC11610559 | biostudies-literature | 2024 Jan-Dec

REPOSITORIES: biostudies-literature