Blood—Brain Barrier Genomics
Open accessAbstract
The blood–brain barrier (BBB) is formed by the brain microvascular endothelium, and the unique transport properties of the BBB are derived from tissue-specific gene expression within this cell. The current studies developed a gene microarray approach specific for the BBB by purifying the initial mRNA from isolated rat brain capillaries to generate tester cDNA. A polymerase chain reaction–based subtraction cloning method, suppression subtractive hybridization (SSH), was used, and the BBB cDNA was subtracted with driver cDNA produced from mRNA isolated from rat liver and kidney. Screening 5% of the subtracted tester cDNA resulted in identification of 50 gene products and more than 80% of those were selectively expressed at the BBB; these included novel gene sequences not found in existing databases, ESTs, and known genes that were not known to be selectively expressed at the BBB. Genes in the latter category include tissue plasminogen activator, insulin-like growth factor-2, PC-3 gene product, myelin basic protein, regulator of G protein signaling 5, utrophin, IκB, connexin-45, the class I major histocompatibility complex, the rat homologue of the transcription factors hbrm or EZH1, and organic anion transporting polypeptide type 2. Knowledge of tissue-specific gene expression at the BBB could lead to new targets for brain drug delivery and could elucidate mechanisms of brain pathology at the microvascular level.
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Pericytes, SMCs, and endothelial cells express thousands of transcripts encoding different transporters, receptors, active efflux pumps, ion channels, and regulatory molecules, whose expression pattern varies by zonation along the arteriocapillary-venous axis and cell type.
“Pericytes, SMCs, and endothelial cells express thousands of transcripts encoding different transporters, receptors, active efflux pumps, ion channels, and regulatory molecules (28, 72, 86, 129, 242, 358, 359, 610, 675, 678), whose expression pattern varies by zonation along the arteriocapillary-venous axis and cell type (610).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [358]
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- Authors
- Li, J. Y., Boado, R. J., & Pardridge, W. M.
- Affiliations
- University of California, Los Angeles (US)
- Department of Medicine, UCLA School of Medicine, Los Angeles, California, U.S.A.
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2001-01
- Volume
- 21
- Issue
- 1
- Pages
- 61-68
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- OpenAlex
- W1972326404
- Cited by
- 164
- References
- 27
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 8 · 2019: 4 · 2018: 7 · 2017: 2 · 2016: 1 · 2015: 6 · 2014: 12 · 2013: 6 · 2012: 8
- FWCI
- 8.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ns038894-04)
- National Institute of Neurological Disorders and Stroke (NS-38894)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- blood-brain barrier, brain microvascular endothelium, tissue-specific gene expression, suppression subtractive hybridization, brain drug delivery, tissue plasminogen activator, insulin-like growth factor II, connexin 45, MHC class I, EZH1
- MeSH terms
- Animals, Blood-Brain Barrier, Brain, Capillaries, Cerebrovascular Circulation, Cloning, Molecular, Glioma, Kidney, Liver, Molecular Sequence Data, Myocardium, Nerve Tissue Proteins, Organ Specificity, RNA, Messenger, Tumor Cells, Cultured, Polymerase Chain Reaction, In Situ Hybridization, Oligonucleotide Array Sequence Analysis, Genomics, Rats
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