{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:41:00Z","timestamp":1790721660796,"version":"4.1.0"},"reference-count":53,"publisher":"American Society for Clinical Investigation","issue":"4","funder":[{"name":"Life Science Investment Fund (LSIF), TEDCO, Maryland","award":["2016-LSIF-3251"],"award-info":[{"award-number":["2016-LSIF-3251"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R21EY026148,R01CA138264,R43EY025903,R01EY028996,R01HL101200,"],"award-info":[{"award-number":["R21EY026148,R01CA138264,R43EY025903,R01EY028996,R01HL101200,"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R44EY025470,F32CA210482"],"award-info":[{"award-number":["R44EY025470,F32CA210482"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"crossref","award":["Dr. H. James"],"award-info":[{"award-number":["Dr. H. James"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"crossref","award":["Carole Free Catalyst Award"],"award-info":[{"award-number":["Carole Free Catalyst Award"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,2,21]]},"abstract":"<jats:p>\n                    The angiopoietin (Ang)\/Tie2 signaling pathway is essential for maintaining vascular homeostasis, and its dysregulation is associated with several diseases. Interactions between Tie2 and \u03b1\n                    <jats:sub>5<\/jats:sub>\n                    \u03b2\n                    <jats:sub>1<\/jats:sub>\n                    integrin have emerged as part of this control; however, the mechanism is incompletely understood. AXT107, a collagen IV\u2013derived peptide, has strong antipermeability activity and has enabled the elucidation of this previously undetermined mechanism. Previously, AXT107 was shown to inhibit VEGFR2 and other growth factor signaling via receptor tyrosine kinase association with specific integrins. AXT107 disrupts \u03b1\n                    <jats:sub>5<\/jats:sub>\n                    \u03b2\n                    <jats:sub>1<\/jats:sub>\n                    and stimulates the relocation of Tie2 and \u03b1\n                    <jats:sub>5<\/jats:sub>\n                    to cell junctions. In the presence of Ang2 and AXT107, junctional Tie2 is activated, downstream survival signals are upregulated, F-actin is rearranged to strengthen junctions, and, as a result, endothelial junctional permeability is reduced. These data suggest that \u03b1\n                    <jats:sub>5<\/jats:sub>\n                    \u03b2\n                    <jats:sub>1<\/jats:sub>\n                    sequesters Tie2 in nonjunctional locations in endothelial cell membranes and that AXT107-induced disruption of \u03b1\n                    <jats:sub>5<\/jats:sub>\n                    \u03b2\n                    <jats:sub>1<\/jats:sub>\n                    promotes clustering of Tie2 at junctions and converts Ang2 into a strong agonist, similar to responses observed when Ang1 levels greatly exceed those of Ang2. The potentiation of Tie2 activation by Ang2 even extended to mouse models in which AXT107 induced Tie2 phosphorylation in a model of hypoxia and inhibited vascular leakage in an Ang2-overexpression transgenic model and an LPS-induced inflammation model. Because Ang2 levels are very high in ischemic diseases, such as diabetic macular edema, neovascular age-related macular degeneration, uveitis, and cancer, targeting \u03b1\n                    <jats:sub>5<\/jats:sub>\n                    \u03b2\n                    <jats:sub>1<\/jats:sub>\n                    with AXT107 provides a potentially more effective approach to treat these diseases.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.122043","type":"journal-article","created":{"date-parts":[[2019,1,22]],"date-time":"2019-01-22T12:55:08Z","timestamp":1548161708000},"source":"Crossref","is-referenced-by-count":53,"title":["A collagen IV\u2013derived peptide disrupts \u03b15\u03b21 integrin and potentiates Ang2\/Tie2 signaling"],"prefix":"10.1172","volume":"4","author":[{"given":"Adam C.","family":"Mirando","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jikui","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel Lima e","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zenny","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas C.","family":"Sass","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria E.","family":"Lorenc","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4176-3808","authenticated-orcid":true,"given":"Jordan J.","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and"},{"name":"Department of Ophthalmology and The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."},{"name":"AsclepiX Therapeutics, Inc., Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Campochiaro","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander S.","family":"Popel","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and"},{"name":"AsclepiX Therapeutics, Inc., Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niranjan B.","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and"},{"name":"AsclepiX Therapeutics, Inc., Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2019,2,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2015.06.002"},{"key":"B2","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2013.00211","article-title":"Vascular permeability and drug delivery in cancers","volume":"3","author":"Azzi","year":"2013","journal-title":"Front Oncol"},{"key":"B3","article-title":"An important role of blood and lymphatic vessels in inflammation and allergy","volume":"2013","author":"Zgraggen","year":"2013","journal-title":"J Allergy (Cairo)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1159\/000078612"},{"issue":"1","key":"B5","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1042\/CS20160129","article-title":"Angiopoietin-Tie signalling in the cardiovascular and lymphatic systems","volume":"131","author":"Eklund","year":"2017","journal-title":"Clin Sci"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2016.278"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81812-7"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1715"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20150718"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163732"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-10-3685"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5322.55"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0070459"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.100059"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2004.10.004"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1172\/JCI84923"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200507082"},{"key":"B18","doi-asserted-by":"crossref","DOI":"10.1038\/srep07139","article-title":"Inhibition of breast cancer growth and metastasis by a biomimetic peptide","volume":"4","author":"Lee","year":"2014","journal-title":"Sci Rep"},{"issue":"373","key":"B19","article-title":"Tyrosine kinase blocking collagen IV-derived peptide suppresses ocular neovascularization and vascular leakage","volume":"9","author":"Silva","year":"2017","journal-title":"Sci Transl Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1714"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1172\/JCI84871"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1172\/JCI74527"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.10128"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-2209fje"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aad9260"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1172\/JCI97488"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000251640.77679.D7"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66549"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.022475"},{"issue":"Pt 8","key":"B30","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1242\/jcs.076935","article-title":"Mesenchymal stem cell migration is regulated by fibronectin through \u03b15\u03b21-integrin-mediated activation of PDGFR-\u03b2 and potentiation of growth factor signals","volume":"124","author":"Veevers-Lowe","year":"2011","journal-title":"J Cell Sci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2121-6-8"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200906044"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.4.882"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200804140"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1941"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003618200"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1216890110"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500292200"},{"key":"B39","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms6962","article-title":"Endothelial destabilization by angiopoietin-2 via integrin \u03b21 activation","volume":"6","author":"Hakanpaa","year":"2015","journal-title":"Nat Commun"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1701821114"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M807920200"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M607771200"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58832"},{"issue":"Pt 2","key":"B44","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1242\/jcs.018556","article-title":"Linking integrin conformation to function","volume":"122","author":"Askari","year":"2009","journal-title":"J Cell Sci"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.4161\/cc.7.3.5234"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2016.278"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1172\/JCI94674"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2016.10.018"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.129.1.203"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/biot.200700169"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.153346"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17808"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.07.052"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/122043\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:34:19Z","timestamp":1779194059000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/122043"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,21]]},"references-count":53,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,2,21]]},"published-print":{"date-parts":[[2019,2,21]]}},"alternative-id":["10.1172\/jci.insight.122043"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.122043","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,21]]},"article-number":"e122043"}}