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Differential expression of receptors mediating receptor-mediated transcytosis (RMT) in brain microvessels, brain parenchyma and peripheral tissues of the mouse and the human

Receptor-mediated transcytosis (RMT) is a principal pathway for transport of macromolecules essential for brain function across the blood–brain barrier (BBB). Antibodies or peptide ligands which bind RMT receptors are often co-opted for brain delivery of biotherapeutics. Constitutively recycling tra...

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Autores principales: Zhang, Wandong, Liu, Qing Yan, Haqqani, Arsalan S., Leclerc, Sonia, Liu, Ziying, Fauteux, François, Baumann, Ewa, Delaney, Christie E., Ly, Dao, Star, Alexandra T., Brunette, Eric, Sodja, Caroline, Hewitt, Melissa, Sandhu, Jagdeep K., Stanimirovic, Danica B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376922/
https://www.ncbi.nlm.nih.gov/pubmed/32698806
http://dx.doi.org/10.1186/s12987-020-00209-0
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author Zhang, Wandong
Liu, Qing Yan
Haqqani, Arsalan S.
Leclerc, Sonia
Liu, Ziying
Fauteux, François
Baumann, Ewa
Delaney, Christie E.
Ly, Dao
Star, Alexandra T.
Brunette, Eric
Sodja, Caroline
Hewitt, Melissa
Sandhu, Jagdeep K.
Stanimirovic, Danica B.
author_facet Zhang, Wandong
Liu, Qing Yan
Haqqani, Arsalan S.
Leclerc, Sonia
Liu, Ziying
Fauteux, François
Baumann, Ewa
Delaney, Christie E.
Ly, Dao
Star, Alexandra T.
Brunette, Eric
Sodja, Caroline
Hewitt, Melissa
Sandhu, Jagdeep K.
Stanimirovic, Danica B.
author_sort Zhang, Wandong
collection PubMed
description Receptor-mediated transcytosis (RMT) is a principal pathway for transport of macromolecules essential for brain function across the blood–brain barrier (BBB). Antibodies or peptide ligands which bind RMT receptors are often co-opted for brain delivery of biotherapeutics. Constitutively recycling transferrin receptor (TfR) is a prototype receptor utilized to shuttle therapeutic cargos across the BBB. Several other BBB-expressed receptors have been shown to mediate transcytosis of antibodies or protein ligands including insulin receptor (INSR) and insulin-like growth factor-1 receptor (IGF1R), lipid transporters LRP1, LDLR, LRP8 and TMEM30A, solute carrier family transporter SLC3A2/CD98hc and leptin receptor (LEPR). In this study, we analyzed expression patterns of genes encoding RMT receptors in isolated brain microvessels, brain parenchyma and peripheral organs of the mouse and the human using RNA-seq approach. IGF1R, INSR and LRP8 were highly enriched in mouse brain microvessels compared to peripheral tissues. In human brain microvessels only INSR was enriched compared to either the brain or the lung. The expression levels of SLC2A1, LRP1, IGF1R, LRP8 and TFRC were significantly higher in the mouse compared to human brain microvessels. The protein expression of these receptors analyzed by Western blot and immunofluorescent staining of the brain microvessels correlated with their transcript abundance. This study provides a molecular transcriptomics map of key RMT receptors in mouse and human brain microvessels and peripheral tissues, important to translational studies of biodistribution, efficacy and safety of antibodies developed against these receptors.
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spelling pubmed-73769222020-08-04 Differential expression of receptors mediating receptor-mediated transcytosis (RMT) in brain microvessels, brain parenchyma and peripheral tissues of the mouse and the human Zhang, Wandong Liu, Qing Yan Haqqani, Arsalan S. Leclerc, Sonia Liu, Ziying Fauteux, François Baumann, Ewa Delaney, Christie E. Ly, Dao Star, Alexandra T. Brunette, Eric Sodja, Caroline Hewitt, Melissa Sandhu, Jagdeep K. Stanimirovic, Danica B. Fluids Barriers CNS Research Receptor-mediated transcytosis (RMT) is a principal pathway for transport of macromolecules essential for brain function across the blood–brain barrier (BBB). Antibodies or peptide ligands which bind RMT receptors are often co-opted for brain delivery of biotherapeutics. Constitutively recycling transferrin receptor (TfR) is a prototype receptor utilized to shuttle therapeutic cargos across the BBB. Several other BBB-expressed receptors have been shown to mediate transcytosis of antibodies or protein ligands including insulin receptor (INSR) and insulin-like growth factor-1 receptor (IGF1R), lipid transporters LRP1, LDLR, LRP8 and TMEM30A, solute carrier family transporter SLC3A2/CD98hc and leptin receptor (LEPR). In this study, we analyzed expression patterns of genes encoding RMT receptors in isolated brain microvessels, brain parenchyma and peripheral organs of the mouse and the human using RNA-seq approach. IGF1R, INSR and LRP8 were highly enriched in mouse brain microvessels compared to peripheral tissues. In human brain microvessels only INSR was enriched compared to either the brain or the lung. The expression levels of SLC2A1, LRP1, IGF1R, LRP8 and TFRC were significantly higher in the mouse compared to human brain microvessels. The protein expression of these receptors analyzed by Western blot and immunofluorescent staining of the brain microvessels correlated with their transcript abundance. This study provides a molecular transcriptomics map of key RMT receptors in mouse and human brain microvessels and peripheral tissues, important to translational studies of biodistribution, efficacy and safety of antibodies developed against these receptors. BioMed Central 2020-07-22 /pmc/articles/PMC7376922/ /pubmed/32698806 http://dx.doi.org/10.1186/s12987-020-00209-0 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zhang, Wandong
Liu, Qing Yan
Haqqani, Arsalan S.
Leclerc, Sonia
Liu, Ziying
Fauteux, François
Baumann, Ewa
Delaney, Christie E.
Ly, Dao
Star, Alexandra T.
Brunette, Eric
Sodja, Caroline
Hewitt, Melissa
Sandhu, Jagdeep K.
Stanimirovic, Danica B.
Differential expression of receptors mediating receptor-mediated transcytosis (RMT) in brain microvessels, brain parenchyma and peripheral tissues of the mouse and the human
title Differential expression of receptors mediating receptor-mediated transcytosis (RMT) in brain microvessels, brain parenchyma and peripheral tissues of the mouse and the human
title_full Differential expression of receptors mediating receptor-mediated transcytosis (RMT) in brain microvessels, brain parenchyma and peripheral tissues of the mouse and the human
title_fullStr Differential expression of receptors mediating receptor-mediated transcytosis (RMT) in brain microvessels, brain parenchyma and peripheral tissues of the mouse and the human
title_full_unstemmed Differential expression of receptors mediating receptor-mediated transcytosis (RMT) in brain microvessels, brain parenchyma and peripheral tissues of the mouse and the human
title_short Differential expression of receptors mediating receptor-mediated transcytosis (RMT) in brain microvessels, brain parenchyma and peripheral tissues of the mouse and the human
title_sort differential expression of receptors mediating receptor-mediated transcytosis (rmt) in brain microvessels, brain parenchyma and peripheral tissues of the mouse and the human
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376922/
https://www.ncbi.nlm.nih.gov/pubmed/32698806
http://dx.doi.org/10.1186/s12987-020-00209-0
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