{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T05:42:14Z","timestamp":1792820534558,"version":"4.5.0"},"reference-count":59,"publisher":"National Academy of Sciences","issue":"23","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Marfans","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"DOI":"10.13039\/501100004099","name":"Ligue Contre le Cancer","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100004099","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["PJT-162099"],"award-info":[{"award-number":["PJT-162099"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010258","name":"Marfan Foundation","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100010258","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002924","name":"Glaucoma Foundation","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100002924","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004431","name":"Fondation de France","doi-asserted-by":"publisher","award":["Bourse Berthe Fouassier"],"award-info":[{"award-number":["Bourse Berthe Fouassier"]}],"id":[{"id":"10.13039\/501100004431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007354","name":"Fondation Lefoulon-Delalande","doi-asserted-by":"crossref","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100007354","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,6,6]]},"abstract":"<jats:p>\n                    Fibrillin-1 is an extracellular matrix protein that assembles into microfibrils which provide critical functions in large blood vessels and other tissues. Mutations in the fibrillin-1 gene are associated with cardiovascular, ocular, and skeletal abnormalities in Marfan syndrome. Here, we reveal that fibrillin-1 is critical for angiogenesis which is compromised by a typical Marfan mutation. In the mouse retina vascularization model, fibrillin-1 is present in the extracellular matrix at the angiogenic front where it colocalizes with microfibril-associated glycoprotein-1, MAGP1. In\n                    <jats:italic>Fbn1<\/jats:italic>\n                    <jats:sup>C1041G\/+<\/jats:sup>\n                    mice, a model of Marfan syndrome, MAGP1 deposition is reduced, endothelial sprouting is decreased, and tip cell identity is impaired. Cell culture experiments confirmed that fibrillin-1 deficiency alters vascular endothelial growth factor-A\/Notch and Smad signaling which regulate the acquisition of endothelial tip cell\/stalk cell phenotypes, and we showed that modulation of MAGP1 expression impacts these pathways. Supplying the growing vasculature of\n                    <jats:italic>Fbn1<\/jats:italic>\n                    <jats:sup>C1041G\/+<\/jats:sup>\n                    mice with a recombinant C-terminal fragment of fibrillin-1 corrects all defects. Mass spectrometry analyses showed that the fibrillin-1 fragment alters the expression of various proteins including ADAMTS1, a tip cell metalloprotease and matrix-modifying enzyme. Our data establish that fibrillin-1 is a dynamic signaling platform in the regulation of cell specification and matrix remodeling at the angiogenic front and that mutant fibrillin-1-induced defects can be rescued pharmacologically using a C-terminal fragment of the protein. These findings, identify fibrillin-1, MAGP1, and ADAMTS1 in the regulation of endothelial sprouting, and contribute to our understanding of how angiogenesis is regulated. This knowledge may have critical implications for people with Marfan syndrome.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2221742120","type":"journal-article","created":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T13:31:38Z","timestamp":1685453498000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":32,"title":["Fibrillin-1 regulates endothelial sprouting during angiogenesis"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6794-1513","authenticated-orcid":false,"given":"Florian","family":"Alonso","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Bordeaux F-33000 Bordeaux, France"},{"name":"INSERM U1026, BioTis F-33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuechao","family":"Dong","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bordeaux F-33000 Bordeaux, France"},{"name":"INSERM U1026, BioTis F-33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2029-3299","authenticated-orcid":false,"given":"Ling","family":"Li","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3A 0C7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8065-7325","authenticated-orcid":false,"given":"Tiya","family":"Jahjah","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bordeaux F-33000 Bordeaux, France"},{"name":"INSERM U1026, BioTis F-33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2448-4797","authenticated-orcid":false,"given":"Jean-William","family":"Dupuy","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bordeaux F-33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3632-6016","authenticated-orcid":false,"given":"Isabelle","family":"Fremaux","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bordeaux F-33000 Bordeaux, France"},{"name":"INSERM U1026, BioTis F-33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6535-9872","authenticated-orcid":false,"given":"Dieter P.","family":"Reinhardt","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3A 0C7, Canada"},{"name":"Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC H3A 0C7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5212-5994","authenticated-orcid":false,"given":"Elisabeth","family":"G\u00e9not","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bordeaux F-33000 Bordeaux, France"},{"name":"INSERM U1026, BioTis F-33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,5,30]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2019.10.002"},{"key":"e_1_3_4_2_2","first-page":"S2","article-title":"Structure of the glomerular mesangium: A biomechanical interpretation","volume":"30","author":"Kriz W.","year":"1990","unstructured":"W. Kriz, M. Elger, K. Lemley, T. Sakai, Structure of the glomerular mesangium: A biomechanical interpretation. Kidney Int. Suppl. 30, S2\u20139 (1990).","journal-title":"Kidney Int. Suppl."},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00795-007-0394-3"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M409882200"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/352337a0"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00298-7"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.039669"},{"key":"e_1_3_4_8_2","first-page":"684","article-title":"The eye in the Marfan syndrome","volume":"79","author":"Maumenee I. H.","year":"1981","unstructured":"I. H. Maumenee, The eye in the Marfan syndrome. Trans. Am. Ophthalmol. Soc. 79, 684\u2013733 (1981).","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1097\/IAE.0000000000003272","article-title":"Characteristics of the foveal microvasculature in children with Marfan syndrome: An optical coherence tomography angiography study","volume":"42","author":"Chen H.","year":"2022","unstructured":"H. Chen , Characteristics of the foveal microvasculature in children with Marfan syndrome: An optical coherence tomography angiography study. Retina 42, 138\u2013151 (2022).","journal-title":"Retina"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.9.9.5"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2019.06.006"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2015.05.002"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200420641"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10908"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05571"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611177104"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.09.016"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.03.025"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.modgep.2006.11.002"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.338103"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom10030488"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2012.02.005"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2012.01.007"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8264"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom12101330"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e08-08-0830"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-230284"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.05.018"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707181"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1192152"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.010540"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206363200"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2018.03.006"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1177\/44.12.8985131"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M600298200"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.176065"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0706335105"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2887-4_20"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-022-04231-3"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom10040596"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-02-270819"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4266"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1369\/0022155411401748"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601400"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27185977"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110583200"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2011.194"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.103028"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.03720"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.304718"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M104533200"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2008.01.001"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2015.05.003"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-007-7166-z"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M504270200"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400212200"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep35956"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00522-7"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1106"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2221742120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T09:21:51Z","timestamp":1695288111000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2221742120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,30]]},"references-count":59,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2023,6,6]]}},"alternative-id":["10.1073\/pnas.2221742120"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2221742120","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,30]]},"assertion":[{"value":"2022-12-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2221742120"}}