The cross-talk between canonical and non-canonical Wnt-dependent pathways regulates P-glycoprotein expression in human blood-brain barrier cells
In 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...
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Nature Publishing Group
2014
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| Acceso en línea: | https://repository.urosario.edu.co/handle/10336/22282 https://doi.org/10.1038/jcbfm.2014.100 |
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ir-10336-222822022-05-02T12:37:13Z The cross-talk between canonical and non-canonical Wnt-dependent pathways regulates P-glycoprotein expression in human blood-brain barrier cells Pinzon-Daza, Martha L. Salaroglio, Iris C Kopecka, Joanna Garzòn, Ruth Couraud, Pierre-Olivier Ghigo, Dario Riganti, Chiara 4 (1 aminoethyl) n (4 pyridyl)cyclohexanecarboxamide Beta catenin Doxorubicin Glycogen synthase kinase 3 Multidrug resistance protein Protein tyrosine phosphatase 1b Rho kinase Rhoa guanine nucleotide binding protein Tyrosine Wnt protein Article Blood brain barrier Coculture Concentration response Controlled study Dephosphorylation Drug efficacy Drug penetration Drug transport Enzyme activation Enzyme inactivation Enzyme inhibition Enzyme phosphorylation Gene silencing Glioblastoma cell line Human Human cell Microvascular endothelial cell Priority journal Protein expression Protein protein interaction Transcription regulation Ubiquitination Wnt signaling pathway Amides Beta catenin Blood-brain barrier Cell survival Coculture techniques Doxorubicin Endothelial cells Glycogen synthase kinase 3 Humans P-glycoprotein Permeability Phosphorylation Protein kinase inhibitors Pyridines Rho-associated kinases Rhoa gtp-binding protein Wnt signaling pathway -catenin Blood-brain barrier Glycogen synthase kinase 3 P-glycoprotein Rhoa kinase Wnt ? non-receptor type 1 tumor Cell line Protein tyrosine phosphatase In 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. 2014 2020-05-25T23:55:58Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 0271678X https://repository.urosario.edu.co/handle/10336/22282 https://doi.org/10.1038/jcbfm.2014.100 eng info:eu-repo/semantics/openAccess application/pdf Nature Publishing Group instname:Universidad del Rosario |
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EdocUR - Universidad del Rosario |
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DSpace |
| language |
Inglés (English) |
| topic |
4 (1 aminoethyl) n (4 pyridyl)cyclohexanecarboxamide Beta catenin Doxorubicin Glycogen synthase kinase 3 Multidrug resistance protein Protein tyrosine phosphatase 1b Rho kinase Rhoa guanine nucleotide binding protein Tyrosine Wnt protein Article Blood brain barrier Coculture Concentration response Controlled study Dephosphorylation Drug efficacy Drug penetration Drug transport Enzyme activation Enzyme inactivation Enzyme inhibition Enzyme phosphorylation Gene silencing Glioblastoma cell line Human Human cell Microvascular endothelial cell Priority journal Protein expression Protein protein interaction Transcription regulation Ubiquitination Wnt signaling pathway Amides Beta catenin Blood-brain barrier Cell survival Coculture techniques Doxorubicin Endothelial cells Glycogen synthase kinase 3 Humans P-glycoprotein Permeability Phosphorylation Protein kinase inhibitors Pyridines Rho-associated kinases Rhoa gtp-binding protein Wnt signaling pathway -catenin Blood-brain barrier Glycogen synthase kinase 3 P-glycoprotein Rhoa kinase Wnt ? non-receptor type 1 tumor Cell line Protein tyrosine phosphatase |
| spellingShingle |
4 (1 aminoethyl) n (4 pyridyl)cyclohexanecarboxamide Beta catenin Doxorubicin Glycogen synthase kinase 3 Multidrug resistance protein Protein tyrosine phosphatase 1b Rho kinase Rhoa guanine nucleotide binding protein Tyrosine Wnt protein Article Blood brain barrier Coculture Concentration response Controlled study Dephosphorylation Drug efficacy Drug penetration Drug transport Enzyme activation Enzyme inactivation Enzyme inhibition Enzyme phosphorylation Gene silencing Glioblastoma cell line Human Human cell Microvascular endothelial cell Priority journal Protein expression Protein protein interaction Transcription regulation Ubiquitination Wnt signaling pathway Amides Beta catenin Blood-brain barrier Cell survival Coculture techniques Doxorubicin Endothelial cells Glycogen synthase kinase 3 Humans P-glycoprotein Permeability Phosphorylation Protein kinase inhibitors Pyridines Rho-associated kinases Rhoa gtp-binding protein Wnt signaling pathway -catenin Blood-brain barrier Glycogen synthase kinase 3 P-glycoprotein Rhoa kinase Wnt ? non-receptor type 1 tumor Cell line Protein tyrosine phosphatase Pinzon-Daza, Martha L. Salaroglio, Iris C Kopecka, Joanna Garzòn, Ruth Couraud, Pierre-Olivier Ghigo, Dario Riganti, Chiara The cross-talk between canonical and non-canonical Wnt-dependent pathways regulates P-glycoprotein expression in human blood-brain barrier cells |
| description |
In 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. |
| format |
Artículo (Article) |
| author |
Pinzon-Daza, Martha L. Salaroglio, Iris C Kopecka, Joanna Garzòn, Ruth Couraud, Pierre-Olivier Ghigo, Dario Riganti, Chiara |
| author_facet |
Pinzon-Daza, Martha L. Salaroglio, Iris C Kopecka, Joanna Garzòn, Ruth Couraud, Pierre-Olivier Ghigo, Dario Riganti, Chiara |
| author_sort |
Pinzon-Daza, Martha L. |
| title |
The cross-talk between canonical and non-canonical Wnt-dependent pathways regulates P-glycoprotein expression in human blood-brain barrier cells |
| title_short |
The cross-talk between canonical and non-canonical Wnt-dependent pathways regulates P-glycoprotein expression in human blood-brain barrier cells |
| title_full |
The cross-talk between canonical and non-canonical Wnt-dependent pathways regulates P-glycoprotein expression in human blood-brain barrier cells |
| title_fullStr |
The cross-talk between canonical and non-canonical Wnt-dependent pathways regulates P-glycoprotein expression in human blood-brain barrier cells |
| title_full_unstemmed |
The cross-talk between canonical and non-canonical Wnt-dependent pathways regulates P-glycoprotein expression in human blood-brain barrier cells |
| title_sort |
cross-talk between canonical and non-canonical wnt-dependent pathways regulates p-glycoprotein expression in human blood-brain barrier cells |
| publisher |
Nature Publishing Group |
| publishDate |
2014 |
| url |
https://repository.urosario.edu.co/handle/10336/22282 https://doi.org/10.1038/jcbfm.2014.100 |
| _version_ |
1740173007569027072 |
| score |
12,131701 |