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The cross-talk between canonical and non-canonical Wnt-dependent pathways regulates P-glycoprotein expression in human blood-brain barrier cells

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dc.creatorPinzon-Daza, Martha L.
dc.creatorSalaroglio, Iris Cspa
dc.creatorKopecka, Joannaspa
dc.creatorGarzòn, Ruthspa
dc.creatorCouraud, Pierre-Olivierspa
dc.creatorGhigo, Dariospa
dc.creatorRiganti, Chiaraspa
dc.date.accessioned2020-05-25T23:55:58Z
dc.date.available2020-05-25T23:55:58Z
dc.date.created2014spa
dc.description.abstractIn this work, we investigate if and how transducers of the 'canonical' Wnt pathway, i.e., Wnt/glycogen synthase kinase 3 (GSK3)/?-catenin, and transducers of the 'non-canonical' Wnt pathway, i.e., Wnt/RhoA/RhoA kinase (RhoAK), cooperate to control the expression of P-glycoprotein (Pgp) in blood-brain barrier (BBB) cells. By analyzing human primary brain microvascular endothelial cells constitutively activated for RhoA, silenced for RhoA or treated with the RhoAK inhibitor Y27632, we found that RhoAK phosphorylated and activated the protein tyrosine phosphatase 1B (PTP1B), which dephosphorylated tyrosine 216 of GSK3, decreasing the GSK3-mediated inhibition of ?-catenin. By contrast, the inhibition of RhoA/RhoAK axis prevented the activation of PTP1B, enhanced the GSK3-induced phosphorylation and ubiquitination of ?-catenin, and reduced the ?-catenin-driven transcription of Pgp. The RhoAK inhibition increased the delivery of Pgp substrates like doxorubicin across the BBB and improved the doxorubicin efficacy against glioblastoma cells co-cultured under a BBB monolayer. Our data demonstrate that in human BBB cells the expression of Pgp is controlled by a cross-talk between canonical and non-canonical Wnt pathways. The disruption of this cross-talk, e.g., by inhibiting RhoAK, downregulates Pgp and increases the delivery of Pgp substrates across the BBB. © 2014 ISCBFM.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1038/jcbfm.2014.100
dc.identifier.issn0271678X
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/22282
dc.language.isoengspa
dc.publisherNature Publishing Groupspa
dc.relation.citationEndPage1269
dc.relation.citationIssueNo. 8
dc.relation.citationStartPage1258
dc.relation.citationTitleJournal of Cerebral Blood Flow and Metabolism
dc.relation.citationVolumeVol. 34
dc.relation.ispartofJournal of Cerebral Blood Flow and Metabolism, ISSN:0271678X, Vol.34, No.8 (2014); pp. 1258-1269spa
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84905510048&doi=10.1038%2fjcbfm.2014.100&partnerID=40&md5=78eb024ed985b5144f04bde45596bc5cspa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subject.keyword4 (1 aminoethyl) n (4 pyridyl)cyclohexanecarboxamidespa
dc.subject.keywordtumoreng
dc.subject.keywordDoxorubicinspa
dc.subject.keywordGlycogen synthase kinase 3spa
dc.subject.keywordMultidrug resistance proteinspa
dc.subject.keywordProtein tyrosine phosphatase 1bspa
dc.subject.keywordRho kinasespa
dc.subject.keywordRhoa guanine nucleotide binding proteinspa
dc.subject.keywordTyrosinespa
dc.subject.keywordWnt proteinspa
dc.subject.keywordArticlespa
dc.subject.keywordBlood brain barrierspa
dc.subject.keywordCoculturespa
dc.subject.keywordConcentration responsespa
dc.subject.keywordControlled studyspa
dc.subject.keywordDephosphorylationspa
dc.subject.keywordDrug efficacyspa
dc.subject.keywordDrug penetrationspa
dc.subject.keywordDrug transportspa
dc.subject.keywordEnzyme activationspa
dc.subject.keywordEnzyme inactivationspa
dc.subject.keywordEnzyme inhibitionspa
dc.subject.keywordEnzyme phosphorylationspa
dc.subject.keywordGene silencingspa
dc.subject.keywordGlioblastoma cell linespa
dc.subject.keywordHumanspa
dc.subject.keywordHuman cellspa
dc.subject.keywordMicrovascular endothelial cellspa
dc.subject.keywordPriority journalspa
dc.subject.keywordProtein expressionspa
dc.subject.keywordProtein protein interactionspa
dc.subject.keywordTranscription regulationspa
dc.subject.keywordUbiquitinationspa
dc.subject.keywordWnt signaling pathwayspa
dc.subject.keywordAmidesspa
dc.subject.keywordBeta cateninspa
dc.subject.keywordBlood-brain barrierspa
dc.subject.keywordCell lineeng
dc.subject.keywordCell survivalspa
dc.subject.keywordCoculture techniquesspa
dc.subject.keywordDoxorubicinspa
dc.subject.keywordEndothelial cellsspa
dc.subject.keywordGlycogen synthase kinase 3spa
dc.subject.keywordHumansspa
dc.subject.keywordP-glycoproteinspa
dc.subject.keywordPermeabilityspa
dc.subject.keywordPhosphorylationspa
dc.subject.keywordProtein kinase inhibitorsspa
dc.subject.keywordProtein tyrosine phosphataseeng
dc.subject.keywordPyridinesspa
dc.subject.keywordRho-associated kinasesspa
dc.subject.keywordRhoa gtp-binding proteinspa
dc.subject.keywordWnt signaling pathwayspa
dc.subject.keyword-cateninspa
dc.subject.keywordBlood-brain barrierspa
dc.subject.keywordGlycogen synthase kinase 3spa
dc.subject.keywordP-glycoproteinspa
dc.subject.keywordRhoa kinasespa
dc.subject.keywordWntspa
dc.subject.keyword?spa
dc.titleThe cross-talk between canonical and non-canonical Wnt-dependent pathways regulates P-glycoprotein expression in human blood-brain barrier cellsspa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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