{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T20:03:36Z","timestamp":1790366616245,"version":"4.1.0"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2013,2,13]],"date-time":"2013-02-13T00:00:00Z","timestamp":1360713600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0055972","type":"journal-article","created":{"date-parts":[[2013,2,13]],"date-time":"2013-02-13T22:28:20Z","timestamp":1360794500000},"page":"e55972","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":114,"title":["Inhibition of Glycogen Synthase Kinase 3\u03b2 Promotes Tight Junction Stability in Brain Endothelial Cells by Half-Life Extension of Occludin and Claudin-5"],"prefix":"10.1371","volume":"8","author":[{"given":"Servio H.","family":"Ramirez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shongshan","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Dykstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slava","family":"Rom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Mercer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy L.","family":"Reichenbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa","family":"Gofman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Persidsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2013,2,13]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s11481-006-9025-3","article-title":"Blood-brain barrier: structural components and function under physiologic and pathologic conditions","volume":"1","author":"Y Persidsky","year":"2006","journal-title":"J Neuroimmune Pharmacol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1089\/ars.2011.3929","article-title":"Tight junctions in brain barriers during central nervous system inflammation","volume":"15","author":"C Coisne","year":"2011","journal-title":"Antioxid Redox Signal"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nrn3114","article-title":"Neurovascular pathways to neurodegeneration in Alzheimer\u2019s disease and other disorders","volume":"12","author":"BV Zlokovic","year":"2011","journal-title":"Nat Rev Neurosci"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s10571-004-1374-y","article-title":"Dynamics of CNS barriers: evolution, differentiation, and modulation","volume":"25","author":"NJ Abbott","year":"2005","journal-title":"Cell Mol Neurobiol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/S1474-4422(07)70326-5","article-title":"Strategies to advance translational research into brain barriers","volume":"7","author":"E Neuwelt","year":"2008","journal-title":"Lancet Neurol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.nbd.2009.07.030","article-title":"Structure and function of the blood-brain barrier","volume":"37","author":"NJ Abbott","year":"2010","journal-title":"Neurobiol Dis"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.2174\/092986710792065090","article-title":"Using small molecule GSK3beta inhibitors to treat inflammation","volume":"17","author":"G Klamer","year":"2010","journal-title":"Curr Med Chem"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.molbrainres.2004.09.003","article-title":"Dishevelled promotes neurite outgrowth in neuronal differentiating neuroblastoma 2A cells, via a DIX-domain dependent pathway","volume":"132","author":"S Fan","year":"2004","journal-title":"Brain Res Mol Brain Res"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.tibs.2009.10.002","article-title":"GSK3: a multifaceted kinase in Wnt signaling","volume":"35","author":"D Wu","year":"2010","journal-title":"Trends Biochem Sci"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.2174\/1389450110607011421","article-title":"Glycogen synthase kinase-3 (GSK3) in psychiatric diseases and therapeutic interventions","volume":"7","author":"RS Jope","year":"2006","journal-title":"Curr Drug Targets"},{"key":"ref11","first-page":"785","article-title":"Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature","volume":"378","author":"DA Cross","year":"1995"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"881","DOI":"10.2353\/ajpath.2010.090671","article-title":"Inhibition of glycogen synthase kinase 3beta (GSK3beta) decreases inflammatory responses in brain endothelial cells","volume":"176","author":"SH Ramirez","year":"2010","journal-title":"Am J Pathol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1096\/fj.01-0870com","article-title":"Hepatocyte growth factor enhances endothelial cell barrier function and cortical cytoskeletal rearrangement: potential role of glycogen synthase kinase-3beta","volume":"16","author":"F Liu","year":"2002","journal-title":"FASEB J"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1083\/jcb.200806024","article-title":"Wnt\/beta-catenin signaling controls development of the blood-brain barrier","volume":"183","author":"S Liebner","year":"2008","journal-title":"J Cell Biol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1172\/JCI0213595","article-title":"Altered vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1-deficient mice","volume":"109","author":"D Graesser","year":"2002","journal-title":"J Clin Invest"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1038\/nrm2717","article-title":"Proximal events in Wnt signal transduction","volume":"10","author":"S Angers","year":"2009","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"pe41","DOI":"10.1126\/scisignal.2002436","article-title":"A WNTer revisit: new faces of beta-catenin and TCFs in pluripotency","volume":"4","author":"K Watanabe","year":"2011","journal-title":"Sci Signal"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"469","DOI":"10.3727\/096504001108747477","article-title":"Involvement of claudin-1 in the beta-catenin\/Tcf signaling pathway and its frequent upregulation in human colorectal cancers","volume":"12","author":"N Miwa","year":"2001","journal-title":"Oncol Res"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.bbrc.2003.12.185","article-title":"Functional crosstalk between Wnt signaling and Cdx-related transcriptional activation in the regulation of the claudin-2 promoter activity","volume":"314","author":"J Mankertz","year":"2004","journal-title":"Biochem Biophys Res Commun"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1091\/mbc.E05-08-0767","article-title":"Cooperation between snail and LEF-1 transcription factors is essential for TGF-beta1-induced epithelial-mesenchymal transition","volume":"17","author":"D Medici","year":"2006","journal-title":"Mol Biol Cell"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1038\/sj.onc.1209902","article-title":"Raf 1 represses expression of the tight junction protein occludin via activation of the zinc-finger transcription factor slug","volume":"26","author":"Z Wang","year":"2007","journal-title":"Oncogene"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1038\/nprot.2010.76","article-title":"Establishment of primary cultures of human brain microvascular endothelial cells to provide an in vitro cellular model of the blood-brain barrier","volume":"5","author":"MJ Bernas","year":"2010","journal-title":"Nat Protoc"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1038\/ncb2373","article-title":"ZNRF1 promotes Wallerian degeneration by degrading AKT to induce GSK3B-dependent CRMP2 phosphorylation","volume":"13","author":"S Wakatsuki","year":"2011","journal-title":"Nat Cell Biol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1126\/science.1160489","article-title":"Global protein stability profiling in mammalian cells","volume":"322","author":"HC Yen","year":"2008","journal-title":"Science"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"505607","DOI":"10.4061\/2011\/505607","article-title":"What Are the bona fide GSK3 Substrates?","volume":"2011","author":"C Sutherland","year":"2011","journal-title":"Int J Alzheimers Dis"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1114\/1.1385811","article-title":"Electrical impedance of cultured endothelium under fluid flow","volume":"29","author":"N DePaola","year":"2001","journal-title":"Ann Biomed Eng"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.1016\/S0006-3495(95)80153-0","article-title":"Impedance analysis of MDCK cells measured by electric cell-substrate impedance sensing","volume":"69","author":"CM Lo","year":"1995","journal-title":"Biophys J"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"16879","DOI":"10.1074\/jbc.M110.186932","article-title":"AMP-activated protein kinase (AMPK) activation and glycogen synthase kinase-3beta (GSK-3beta) inhibition induce Ca2+-independent deposition of tight junction components at the plasma membrane","volume":"286","author":"L Zhang","year":"2011","journal-title":"J Biol Chem"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.bbrc.2010.05.164","article-title":"Glycogen Synthase Kinase 3 (GSK-3) influences epithelial barrier function by regulating occludin, claudin-1 and E-cadherin expression","volume":"397","author":"EA Severson","year":"2010","journal-title":"Biochem Biophys Res Commun"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s00232-007-9054-8","article-title":"The connexin turnover, an important modulating factor of the level of cell-to-cell junctional communication: comparison with other integral membrane proteins","volume":"217","author":"JC Herve","year":"2007","journal-title":"J Membr Biol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"F436","DOI":"10.1152\/ajprenal.00674.2009","article-title":"Nedd4-2 interacts with occludin to inhibit tight junction formation and enhance paracellular conductance in collecting duct epithelia","volume":"299","author":"NS Raikwar","year":"2010","journal-title":"Am J Physiol Renal Physiol"},{"key":"ref32","doi-asserted-by":"crossref","unstructured":"Mandel I, Paperna T, Volkowich A, Merhav M, Glass-Marmor L, <etal>et al<\/etal>.. (2012) The ubiquitin-proteasome pathway regulates claudin 5 degradation. J Cell Biochem.","DOI":"10.1002\/jcb.24118"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"21036","DOI":"10.1074\/jbc.M109.016766","article-title":"Occludin phosphorylation and ubiquitination regulate tight junction trafficking and vascular endothelial growth factor-induced permeability","volume":"284","author":"T Murakami","year":"2009","journal-title":"J Biol Chem"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1210\/me.2007-0143","article-title":"Glucocorticoid-induced degradation of glycogen synthase kinase-3 protein is triggered by serum- and glucocorticoid-induced protein kinase and Akt signaling and controls beta-catenin dynamics and tight junction formation in mammary epithelial tumor cells","volume":"21","author":"KL Failor","year":"2007","journal-title":"Mol Endocrinol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1083\/jcb.132.3.451","article-title":"Catenins and zonula occludens-1 form a complex during early stages in the assembly of tight junctions","volume":"132","author":"AK Rajasekaran","year":"1996","journal-title":"J Cell Biol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"5040","DOI":"10.1210\/en.2002-0139","article-title":"Catenins in the rat epididymis: their expression and regulation in adulthood and during postnatal development","volume":"144","author":"S DeBellefeuille","year":"2003","journal-title":"Endocrinology"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"10201","DOI":"10.1074\/jbc.M111384200","article-title":"The tight junction-specific protein occludin is a functional target of the E3 ubiquitin-protein ligase itch","volume":"277","author":"A Traweger","year":"2002","journal-title":"J Biol Chem"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"14440","DOI":"10.1073\/pnas.251541198","article-title":"Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy","volume":"98","author":"MD Gomes","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"E145","DOI":"10.1152\/ajpendo.00085.2006","article-title":"IGF-I does not prevent myotube atrophy caused by proinflammatory cytokines despite activation of Akt\/Foxo and GSK-3beta pathways and inhibition of atrogin-1 mRNA","volume":"292","author":"M Dehoux","year":"2007","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"6282","DOI":"10.4049\/jimmunol.0804093","article-title":"CCR7-dependent stimulation of survival in dendritic cells involves inhibition of GSK3beta","volume":"183","author":"C Escribano","year":"2009","journal-title":"J Immunol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1242\/jcs.040055","article-title":"The E3 ubiquitin ligase LNX1p80 promotes the removal of claudins from tight junctions in MDCK cells","volume":"122","author":"S Takahashi","year":"2009","journal-title":"J Cell Sci"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0055972","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T21:14:34Z","timestamp":1745961274000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0055972"}},"subtitle":[],"editor":[{"given":"Sebastian","family":"Grundmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,2,13]]},"references-count":41,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2013,2,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0055972","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,13]]}}}