miR‐21 represses FasL in microglia and protects against microglia‐mediated neuronal cell death following hypoxia/ischemia
Abstract
A growing body of evidence suggests that microRNA (miRNA) dysregulation contributes to many types of human disease, including central nervous system disorders. In this study, we identified an inverse correlation between the expression of miR‐21 and Fas ligand (FasL) during hypoxia‐induced microglial activation. Specifically, hypoxia caused the upregulation of FasL expression but the downregulation of miR‐21 expression in microglia. Furthermore, we demonstrated that miR‐21 suppresses FasL production by directly binding to its 3′‐untranslated region. The overproduction of FasL following hypoxic microglial activation induced neuronal apoptosis, whereas the ectopic expression of miR‐21 partially protected neurons from cell death caused by hypoxia‐activated microglia. Finally, we confirmed that the function of miR‐21 in microglia‐mediated neuronal injury is dependent on FasL. Our study demonstrates an important role for miRNAs in microglia‐mediated neuronal apoptosis, and suggests potential novel therapeutic interventions for cerebral hypoxic diseases associated with microglial activation. © 2012 Wiley Periodicals, Inc.
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Some evidence directly points to the neurotoxic effect of microglial FasL and its repression by microglial miR-21.
“Consistent with this, some evidence directly points to the neurotoxic effect of microglial FasL and its repression by microglial miR-2120, but this has yet to be investigated in the context of spinal cord injury.”
From CNS microRNA profiles: a database for cell type enriched microRNA expression across the mouse central nervous system (2020) · cites this paper as [20]
Cites
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MicroRNA‐21 protects neurons from ischemic death
Buller, B., Liu, X., Wang, X., Zhang, R. L., Zhang, L., Hozeska‐Solgot, A., Chopp, M., & Zhang, Z. G. (2010) · The FEBS Journal · doi:10.1111/j.1742-4658.2010.07818.x · Cited by 242 · cited 1× · see citing works
“…between the dysregulation of miRNA and microglia-mediated neuronal apoptosis; therefore, we evaluated miR-21 in microglia, although it has been studied in cancer cells (Wang and Li, 2010), cardiac myocytes (Sayed et al., 2010), and neuronal cells (Buller et al., 2010; Ziu et al., 2011).”
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Harrison, E. B., Hochfelder, C. G., Lamberty, B. G., Meays, B. M., Morsey, B. M., Kelso, M. L., Fox, H. S., & Yelamanchili, S. V. (2016) · FEBS Open Bio · doi:10.1002/2211-5463.12092 · Cited by 151 · see citing works
Profile of Cerebrospinal microRNAs in Fibromyalgia
Bjersing, J. L., Lundborg, C., Bokarewa, M. I., & Mannerkorpi, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0078762 · Cited by 98 · see citing works
MicroRNA Expression in the Glaucomatous Retina
Jayaram, H., Cepurna, W. O., Johnson, E. C., & Morrison, J. C. (2015) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.15-18088 · Cited by 60 · see citing works
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Induction of miR-155 after Brain Injury Promotes Type 1 Interferon and has a Neuroprotective Effect
Harrison, E. B., Emanuel, K., Lamberty, B. G., Morsey, B. M., Li, M., Kelso, M. L., Yelamanchili, S. V., & Fox, H. S. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00228 · Cited by 48 · see citing works
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miR-142-3p Regulates BDNF Expression in Activated Rodent Microglia Through Its Target CAMK2A
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- Authors
- Zhang, L., Dong, L., Li, Y., Hong, Z., & Wei, W.
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2012-08-20
- Volume
- 60
- Issue
- 12
- Pages
- 1888-1895
- ISSN
- 0894-1491
- 1098-1136
- Cited by
- 103
- References
- 2
- Language
- en
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