{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:15:58Z","timestamp":1777392958214,"version":"3.51.4"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,11,5]],"date-time":"2018-11-05T00:00:00Z","timestamp":1541376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["1R01GM120592"],"award-info":[{"award-number":["1R01GM120592"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA023108\u201036"],"award-info":[{"award-number":["P30CA023108\u201036"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["16GRNT27260362"],"award-info":[{"award-number":["16GRNT27260362"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Endothelial diaphragms are subcellular structures critical for mammalian survival with poorly understood biogenesis. Plasmalemma vesicle associated protein (<jats:styled-content style=\"fixed-case\">PLVAP<\/jats:styled-content>) is the only known diaphragm component and is necessary for diaphragm formation. Very little is known about <jats:styled-content style=\"fixed-case\">PLVAP<\/jats:styled-content> regulation. Phorbol esters (<jats:styled-content style=\"fixed-case\">PMA<\/jats:styled-content>) are known to induce de novo <jats:styled-content style=\"fixed-case\">PLVAP<\/jats:styled-content> expression and diaphragm formation. We show that this induction relies on the de novo production of soluble factors that will act in an autocrine manner to induce <jats:styled-content style=\"fixed-case\">PLVAP<\/jats:styled-content> transcription and protein expression. We identified vascular endothelial growth factor\u2010A (<jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\u2010A) signalling through <jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content>2 as a necessary but not sufficient downstream event as <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\u2010A inhibition with antibodies and si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> or pharmacological inhibition of <jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content>2 only partially inhibit <jats:styled-content style=\"fixed-case\">PLVAP<\/jats:styled-content> upregulation. In terms of downstream pathways, inhibition of <jats:styled-content style=\"fixed-case\">MEK<\/jats:styled-content>1\/Erk1\/2 <jats:styled-content style=\"fixed-case\">MAP<\/jats:styled-content> kinase blocked <jats:styled-content style=\"fixed-case\">PLVAP<\/jats:styled-content> upregulation, whereas inhibition of p38 and <jats:styled-content style=\"fixed-case\">JNK MAP<\/jats:styled-content> kinases or <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K and Akt had no effect on <jats:styled-content style=\"fixed-case\">PMA<\/jats:styled-content>\u2010induced <jats:styled-content style=\"fixed-case\">PLVAP<\/jats:styled-content> expression. In conclusion, we show that <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\u2010A along with other secreted proteins act synergistically to up\u2010regulate <jats:styled-content style=\"fixed-case\">PLVAP<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">MEK<\/jats:styled-content>1\/Erk1\/2 dependent manner, bringing us one step further into understanding the genesis of the essential structures that are endothelial diaphragms.<\/jats:p>","DOI":"10.1111\/jcmm.13993","type":"journal-article","created":{"date-parts":[[2018,11,5]],"date-time":"2018-11-05T12:07:45Z","timestamp":1541419665000},"page":"920-933","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Phorbol esters induce <scp>PLVAP<\/scp> expression via <scp>VEGF<\/scp> and additional secreted molecules in <scp>MEK<\/scp>1\u2010dependent and p38, <scp>JNK<\/scp> and <scp>PI<\/scp>3K\/Akt\u2010independent manner"],"prefix":"10.1111","volume":"23","author":[{"given":"B. JoNell","family":"Hamilton","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Cell Biology Geisel School of Medicine at Dartmouth Lebanon New Hampshire"},{"name":"Norris Cotton Cancer Center Geisel School of Medicine at Dartmouth Lebanon New Hampshire"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Tse","sequence":"additional","affiliation":[{"name":"Department of Pathology Geisel School of Medicine at Dartmouth Lebanon New Hampshire"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2969-1725","authenticated-orcid":false,"given":"Radu V.","family":"Stan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology Geisel School of Medicine at Dartmouth Lebanon New Hampshire"},{"name":"Norris Cotton Cancer Center Geisel School of Medicine at Dartmouth Lebanon New Hampshire"},{"name":"Department of Pathology Geisel School of Medicine at Dartmouth Lebanon New Hampshire"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2007.00075.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1253447"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2012.11.003"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-012-0987-3"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3101"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2015.05.001"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2018-105262"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2018-105299"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-11-188763"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501859"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19814"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2000.6489"},{"key":"e_1_2_8_14_1","first-page":"96A\u2010A","article-title":"Purification and cloning of PV\u20101, a novel caveolar protein of the rat microvasculature","volume":"9","author":"Stan R","year":"1998","journal-title":"Mol Biol Cell"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.23.13203"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032655"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E03-08-0593"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603501103"},{"key":"e_1_2_8_19_1","first-page":"86","article-title":"Phorbol ester induces diaphragmed fenestrae in large vessel endothelium in\u00a0vitro","volume":"44","author":"Lombardi T","year":"1987","journal-title":"Eur J Cell Biol"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4889(83)90039-3"},{"key":"e_1_2_8_21_1","first-page":"765","article-title":"Neovasculature induced by vascular endothelial growth factor is fenestrated","volume":"57","author":"Roberts WG","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.108.6.2369"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000055324.34758.32"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000118600.91698.BB"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.101564798"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700436"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01902"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17423"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(03)00378-6"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00133.2005"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1805"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.5.17.3217"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.5.17.3216"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-7146"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-1731"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI76431"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200806024"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2006.08.020"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-018-9599-4"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.06.022"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-05389-8"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00909.2003"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.4915"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.304"},{"key":"e_1_2_8_46_1","volume-title":"Essentials of Glycobiology","author":"Jeffrey D","year":"2009"},{"key":"e_1_2_8_47_1","first-page":"285","article-title":"Subunit structure and enzymic activity of pertussis toxin","volume":"5","author":"Burns DL","year":"1988","journal-title":"Microbiol Sci"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032713-120145"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2479986"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.52.31189"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.104.5.1423"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.87"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjcmm.13993","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.13993","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T08:21:10Z","timestamp":1694679670000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.13993"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,5]]},"references-count":51,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["10.1111\/jcmm.13993"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.13993","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,5]]},"assertion":[{"value":"2018-09-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}