{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T04:02:40Z","timestamp":1793678560588,"version":"4.5.1"},"reference-count":39,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,5,18]],"date-time":"2012-05-18T00:00:00Z","timestamp":1337299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL070738"],"award-info":[{"award-number":["HL070738"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY018158"],"award-info":[{"award-number":["EY018158"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 DK074367"],"award-info":[{"award-number":["T32 DK074367"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY005587"],"award-info":[{"award-number":["EY005587"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY021721"],"award-info":[{"award-number":["EY021721"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007698","name":"University of Florida","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007698","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Blood vessels are formed during development and tissue repair through a plethora of modifiers that coordinate efficient vessel assembly in various cellular settings. Here we used the yeast 2\u2010hybrid approach and demonstrated a broad affinity of connective tissue growth factor (CCN2\/CTGF) to C\u2010terminal cystine knot motifs present in key angiogenic regulators Slit3, von Willebrand factor, platelet\u2010derived growth factor\u2010B, and VEGF\u2010A. Biochemical characterization and histological analysis showed close association of CCN2\/CTGF with these regulators in murine angiogenesis models: normal retinal development, oxygen\u2010induced retinopathy (OIR), and Lewis lung carcinomas. CCN2\/CTGF and Slit3 proteins worked in concert to promote\n                    <jats:italic>in vitro<\/jats:italic>\n                    angiogenesis and downstream Cdc42 activation. A fragment corresponding to the first three modules of CCN2\/CTGF retained this broad binding ability and gained a dominant\u2010negative function. Intravitreal injection of this mutant caused a significant reduction in vascular obliteration and retinal neovascularization\n                    <jats:italic>vs<\/jats:italic>\n                    . saline injection in the OIR model. Knocking down\n                    <jats:italic>CCN2\/CTGF<\/jats:italic>\n                    expression by short\u2010hairpin RNA or ectopic expression of this mutant greatly decreased tumorigenesis and angiogenesis. These results provided mechanistic insight into the angiogenic action of CCN2\/CTGF and demonstrated the therapeutic potential of dominant\u2010negative CCN2\/CTGF mutants for antiangiogenesis.\u2014Pi, L., Shenoy, A. K., Liu, J., Kim, S., Nelson, N., Xia, H., Hauswirth, W. W., Petersen, B. E., Schultz, G. S., Scott, E. W. CCN2\/CTGF regulates neovessel formation\n                    <jats:italic>via<\/jats:italic>\n                    targeting structurally conserved cystine knot motifs in multiple angiogenic regulators.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    26, 3365\u20133379 (2012).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.11-200154","type":"journal-article","created":{"date-parts":[[2012,5,20]],"date-time":"2012-05-20T11:25:22Z","timestamp":1337513122000},"page":"3365-3379","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["CCN2\/CTGF regulates neovessel formation\n                    <i>via<\/i>\n                    targeting structurally conserved cystine knot motifs in multiple angiogenic regulators"],"prefix":"10.1096","volume":"26","author":[{"given":"Liya","family":"Pi","sequence":"first","affiliation":[{"name":"Program in Stem Cell Biology and Regenerative Medicine University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anitha K.","family":"Shenoy","sequence":"additional","affiliation":[{"name":"Program in Stem Cell Biology and Regenerative Medicine University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungbum","family":"Kim","sequence":"additional","affiliation":[{"name":"Program in Stem Cell Biology and Regenerative Medicine University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikole","family":"Nelson","sequence":"additional","affiliation":[{"name":"Program in Stem Cell Biology and Regenerative Medicine University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiming","family":"Xia","sequence":"additional","affiliation":[{"name":"Program in Stem Cell Biology and Regenerative Medicine University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W.","family":"Hauswirth","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryon E.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Institute for Regenerative Medicine Wake Forest University  Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory S.","family":"Schultz","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward W.","family":"Scott","sequence":"additional","affiliation":[{"name":"Program in Stem Cell Biology and Regenerative Medicine University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,5,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-008-9107-3"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2008.03203.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3599"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22079"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.03.081"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2008.01.002"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.114.6.1285"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.4.2958"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1159\/000055339"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0332fje"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00505"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-7870"},{"key":"e_1_2_7_14_1","first-page":"101","article-title":"Oxygen\u2010induced retinopathy in the mouse","volume":"35","author":"Smith L. E.","year":"1994","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.187"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-12-193326"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V65.1.85.85"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-01-264507"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90127-C"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend.15.5.0639"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb826"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1653708"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.02.001"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(03)00161-8"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-1546fje"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2008.142646"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30074"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-009-0053-7"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-1415"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.20.2108"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvn159"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21433"},{"key":"e_1_2_7_33_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0030562","article-title":"CCN2\/connective tissue growth factor is essential for pericyte adhesion and endothelial basement membrane formation during angiogenesis","volume":"7","author":"Hall\u2010Glenn F.","year":"2012","journal-title":"PLoS One"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00667-10"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1742"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63813-8"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.20.2.189"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.04.010"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20022027"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.225755"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.11-200154","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.11-200154","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.11-200154","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T17:10:07Z","timestamp":1761671407000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.11-200154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,5,18]]},"references-count":39,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2012,8]]}},"alternative-id":["10.1096\/fj.11-200154"],"URL":"https:\/\/doi.org\/10.1096\/fj.11-200154","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,5,18]]},"assertion":[{"value":"2012-01-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-05-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-05-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}