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

Fluids and Barriers of the CNS
Wandong ZhangDanica B. Stanimirovic

Abstract

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 micr...Continue Reading

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Citations

Dec 16, 2020·Advanced Drug Delivery Reviews·M Masmudi-MartínM Valiente
Mar 3, 2021·Nature Reviews. Drug Discovery·Georg C TerstappenWandong Zhang
Oct 16, 2020·Fluids and Barriers of the CNS·Y WoutersM Dewilde

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Methods Mentioned

BETA
RNA-seq
surgical resections
Assay
RNASeq
single-cell sequencing
single cell sequencing
transgenic

Software Mentioned

Sequence Read Archive
FASTX toolkit
GDC
ProteinSimple
DESeq
STAR
Genomics Data Commons
Wes
RSEM

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