Neostatin-7 regulates bFGF-induced corneal lymphangiogenesis.
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.
Kojima
Takashi
T
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA.
Azar
Dimitri T
DT
Chang
Jin-Hong
JH
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D043170:Collagen Type XVIII / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D003315:Cornea / Q000187:drug effects*; D016510:Corneal Neovascularization / Q000188:drug therapy; D048988:Corneal Surgery, Laser; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D042583:Lymphangiogenesis / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000737:chemistry / Q000235:genetics; D014947:Wounds and Injuries / Q000503:physiopathology
D020533:Angiogenesis Inhibitors; D043170:Collagen Type XVIII; D010446:Peptide Fragments; D011994:Recombinant Proteins; C503329:neostatin-7 protein, mouse; C108111:fibroblast growth factor 13; D005346:Fibroblast Growth Factors; D040321:Vascular Endothelial Growth Factor Receptor-3