SCF (Stem Cell Factor) and cKIT Modulate Pathological Ocular Neovascularization

• DOI: 10.1161/atvbaha.119.313179
• Publication Date: 2019-08-22T09:00:34Z
• Authors: Koung Li Kim; Songyi Seo; Jee Taek Kim; Jaetaek Kim; Won Kim; Yeongju Yeo; Jong-Hyuk Sung; Sang Gyu Park; Wonhee Suh
• Keywords: Male; 0301 basic medicine; Analysis of Variance; Stem Cell Factor; Endothelial Cells; Angiogenesis Inhibitors; Enzyme-Linked Immunosorbent Assay; Retinal Neovascularization; Immunohistochemistry; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; Mice; Proto-Oncogene Proteins c-kit; 03 medical and health sciences; Gene Expression Regulation; Retinal Diseases; Animals; Humans; Female; Hypoxia; Cells, Cultured; Signal Transduction

Aberrant neovascularization is a leading cause of blindness in several eye diseases, including age-related macular degeneration and proliferative diabetic retinopathy. The identification key regulators pathological ocular has been subject extensive research great therapeutic interest. Here, we explored the previously unrecognized role cKIT its ligand, SCF (stem cell factor), process. Approach Results: Compared with normoxia, hypoxia, crucial driver neovascularization, caused to be highly upregulated endothelial cells, which significantly enhanced angiogenic response cells SCF. In murine models such as oxygen-induced retinopathy laser-induced choroidal models, expression was increased tissues, blockade using cKit mutant mice anti-SCF neutralizing IgG substantially suppressed neovascularization. Mechanistically, SCF/cKIT signaling induced through phosphorylation glycogen synthase kinase-3β enhancement nuclear translocation β-catenin transcription target genes related angiogenesis. Inhibition β-catenin-mediated chemical inhibitors blocked SCF-induced vitro angiogenesis injection agonist into retina. Conclusions; Our data reveal that are promising novel targets for treating vision-threatening neovascular diseases.