Neostatin‐7 regulates bFGF‐induced corneal lymphangiogenesis

Abstract
Neostatin‐7, with an anti‐angiogenic potential, is generated from the proteolytic action of matrix metalloproteinase‐7 on collagen XVIII. We previously reported that neostatin‐7 inhibited angiogenesis in vitro and in vivo. Here we demonstrate that neostatin‐7/collagen XVIII may possess anti‐lymphangiogenic activities by: (1) corneal micropellet implantation of neostatin‐7 reduced bFGF‐induced corneal lymphangiogenesis; (2) neostatin‐7 bound to VEGF receptor‐3 in vitro; and (3) enhanced corneal lymphangiogenesis and VEGF‐C expression in collagen XVIII knockout mice in a corneal wounding model. Understanding the mechanism of neostatin‐7/collagen XVIII on corneal lymphangiogenesis may provide therapeutic interventions to treat lymphangiogenesis‐related disorders, such as lymphedema, transplantation rejection and cancers.