miR-98 and let-7g* protect the blood-brain barrier under neuroinflammatory conditions
Open accessAbstract
Pathologic conditions in the central nervous system, regardless of the underlying injury mechanism, show a certain level of blood-brain barrier (BBB) impairment. Endothelial dysfunction is the earliest event in the initiation of vascular damage caused by inflammation due to stroke, atherosclerosis, trauma, or brain infections. Recently, microRNAs (miRNAs) have emerged as a class of gene expression regulators. The relationship between neuroinflammation and miRNA expression in brain endothelium remains unexplored. Previously, we showed the BBB-protective and anti-inflammatory effects of glycogen synthase kinase (GSK) 3β inhibition in brain endothelium in in vitro and in vivo models of neuroinflammation. Using microarray screening, we identified miRNAs induced in primary human brain microvascular endothelial cells after exposure to the pro-inflammatory cytokine, tumor necrosis factor-α, with/out GSK3β inhibition. Among the highly modified miRNAs, let-7 and miR-98 were predicted to target the inflammatory molecules, CCL2 and CCL5. Overexpression of let-7 and miR-98 in vitro and in vivo resulted in reduced leukocyte adhesion to and migration across endothelium, diminished expression of pro-inflammatory cytokines, and increased BBB tightness, attenuating barrier ‘leakiness’ in neuroinflammation conditions. For the first time, we showed that miRNAs could be used as a therapeutic tool to prevent the BBB dysfunction in neuroinflammation.
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miR-98 reduces the endothelial pro-inflammatory response by directly targeting MCP-1/CCL2 and CCL5/RANTES.
“Additionally, miR-98 reduces the endothelial pro-inflammatory response by direct targeting monocyte chemotactic protein-1 (MCP-1)/CCL2 and CCL5/RANTES [253].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [253]
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Cited by
Sorted by citations
Yang, J., Cao, L.-L., Wang, X.-P., Guo, W., Guo, R.-B., Sun, Y.-Q., Xue, T.-F., Cai, Z.-Y., Ji, J., Cheng, H., et al. (2021) · Cell Death & Disease · doi:10.1038/s41419-020-03310-2 · Cited by 73 · see citing works
MicroRNAs as Regulators of Phagocytosis
Gierlikowski, W., & Gierlikowska, B. (2022) · Cells · doi:10.3390/cells11091380 · Cited by 25 · see citing works
- Authors
- Rom, S., Dykstra, H., Zuluaga-Ramirez, V., Reichenbach, N. L., & Persidsky, Y.
- Affiliations
- Temple University (US)
- Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA. Correspondence: Dr S Rom, Department of Pathology and Laboratory Medicine, Temple University School of Medicine, 3500 North Broad Street, Medical Education and Research Building, Room 807, Philadelphia, Pennsylvania 19140, USA
- Corresponding author
- Rom, Slava
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2015-07-01
- Volume
- 35
- Issue
- 12
- Pages
- 1957-1965
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- PMC
- PMC4671116
- OpenAlex
- W2468923595
- Cited by
- 118
- References
- 2
- Citations by year
- 2026: 8 · 2025: 4 · 2024: 7 · 2023: 12 · 2022: 15 · 2021: 10 · 2020: 21 · 2019: 10 · 2018: 7 · 2017: 10 · 2016: 11 · 2015: 3
- FWCI
- 5.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R37AA015913, AA015913, R01AA015913)
- National Institute of Mental Health (MH65151, R01MH065151)
- National Institute of Neurological Disorders and Stroke (R21NS087385, NS087385)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- miR-98, let-7g, blood-brain barrier, neuroinflammation, microRNA, brain microvascular endothelial cells, GSK-3β inhibition, TNF-α, MCP-1, RANTES, leukocyte adhesion, inflammatory cytokines, endothelial dysfunction
- MeSH terms
- Animals, Blood-Brain Barrier, Capillaries, Capillary Permeability, Cell Adhesion, Cell Movement, Inflammation, Male, Mice, Inbred C57BL, Transfection, Tumor Necrosis Factor-alpha, Chemokine CCL2, Chemokine CCL5, MicroRNAs, Glycogen Synthase Kinase 3, Endothelial Cells, Microarray Analysis, Mice
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