{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:49:32Z","timestamp":1791298172567,"version":"4.1.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:sec>\n            <jats:title>Objective:<\/jats:title>\n            <jats:p>Aberrant neovascularization is a leading cause of blindness in several eye diseases, including age-related macular degeneration and proliferative diabetic retinopathy. The identification of key regulators of pathological ocular neovascularization has been a subject of extensive research and great therapeutic interest. Here, we explored the previously unrecognized role of cKIT and its ligand, SCF (stem cell factor), in the pathological ocular neovascularization process.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results:<\/jats:title>\n            <jats:p>\n              Compared with normoxia, hypoxia, a crucial driver of neovascularization, caused cKIT to be highly upregulated in endothelial cells, which significantly enhanced the angiogenic response of endothelial cells to SCF. In murine models of pathological ocular neovascularization, such as oxygen-induced retinopathy and laser-induced choroidal neovascularization models, cKIT and SCF expression was significantly increased in ocular tissues, and blockade of cKIT and SCF using\n              <jats:italic>cKit<\/jats:italic>\n              mutant mice and anti-SCF neutralizing IgG substantially suppressed pathological ocular neovascularization. Mechanistically, SCF\/cKIT signaling induced neovascularization through phosphorylation of glycogen synthase kinase-3\u03b2 and enhancement of the nuclear translocation of \u03b2-catenin and the transcription of \u03b2-catenin target genes related to angiogenesis. Inhibition of \u03b2-catenin-mediated transcription using chemical inhibitors blocked SCF-induced in vitro angiogenesis in hypoxia, and injection of a \u03b2-catenin agonist into\n              <jats:italic>cKit<\/jats:italic>\n              mutant mice with oxygen-induced retinopathy significantly enhanced pathological neovascularization in the retina.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions;<\/jats:title>\n            <jats:p>Our data reveal that SCF and cKIT are promising novel therapeutic targets for treating vision-threatening ocular neovascular diseases.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.119.313179","type":"journal-article","created":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T09:00:34Z","timestamp":1566464434000},"page":"2120-2131","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":37,"title":["SCF (Stem Cell Factor) and cKIT Modulate Pathological Ocular Neovascularization"],"prefix":"10.1161","volume":"39","author":[{"given":"Koung Li","family":"Kim","sequence":"first","affiliation":[{"name":"From the College of Pharmacy (K.L.K., S.S., Y.Y., W.S.), Chung-Ang University, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songyi","family":"Seo","sequence":"additional","affiliation":[{"name":"From the College of Pharmacy (K.L.K., S.S., Y.Y., W.S.), Chung-Ang University, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jee Taek","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology (J.T.K.), Chung-Ang University, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaetaek","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine (J.K.), Chung-Ang University, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea (W.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeongju","family":"Yeo","sequence":"additional","affiliation":[{"name":"From the College of Pharmacy (K.L.K., S.S., Y.Y., W.S.), Chung-Ang University, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Hyuk","family":"Sung","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Yonsei University, Incheon, Korea (J.-H.S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Gyu","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Ajou University, Suwon, Korea (S.G.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonhee","family":"Suh","sequence":"additional","affiliation":[{"name":"From the College of Pharmacy (K.L.K., S.S., Y.Y., W.S.), Chung-Ang University, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2015.06.002"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-202x.2001.00006.x"},{"key":"e_1_3_4_4_2","first-page":"599","article-title":"The role of stem cell factor and of alternative c-kit gene products in the establishment, maintenance and function of germ cells.","volume":"44","author":"Sette C","year":"2000","unstructured":"Sette, C, Dolci, S, Geremia, R, Rossi, P. 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