MicroRNA-21 Regulates Astrocytic Response Following Spinal Cord Injury
Open accessAbstract
Astrogliosis following spinal cord injury (SCI) involves an early hypertrophic response that serves to repair damaged blood-brain barrier and a subsequent hyperplastic response that results in a dense scar that impedes axon regeneration. The mechanisms regulating these two phases of astrogliosis are beginning to be elucidated. In this study, we found that microRNA-21 (miR-21) increases in a time-dependent manner following SCI in mouse. Astrocytes adjacent to the lesion area express high levels of miR-21 whereas astrocytes in uninjured spinal cord express low levels of miR-21. To study the role of miR-21 in astrocytes after SCI, transgenic mice were generated that conditionally overexpress either the primary miR-21 transcript in astrocytes or a miRNA sponge designed to inhibit miR-21 function. Overexpression of miR-21 in astrocytes attenuated the hypertrophic response to SCI. Conversely, expression of the miR-21 sponge augmented the hypertrophic phenotype, even in chronic stages of SCI recovery when astrocytes have normally become smaller in size with fine processes. Inhibition of miR-21 function in astrocytes also resulted in increased axon density within the lesion site. These findings demonstrate a novel role for miR-21 in regulating astrocytic hypertrophy and glial scar progression after SCI, and suggest miR-21 as a potential therapeutic target for manipulating gliosis and enhancing functional outcome.
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miR-21 expression in astrocytes following injury both promoted glial scar formation and hindered axonal regrowth.
“One study demonstrated miR-21 expression in astrocytes following injury both promoted glial scar formation and hindered axonal regrowth, underscoring the importance of cell types beyond neurons in the miR-21 injury response19.”
From CNS microRNA profiles: a database for cell type enriched microRNA expression across the mouse central nervous system (2020) · cites this paper as [19]
The Introduction and Discussion report increased miR-21 in astrocytes after spinal cord injury and a role in glial-scar progression. But they do not establish that miR-21 promotes scar formation: overexpression attenuated astrocytic hypertrophy. The Results found more axons in lesions when miR-21 was inhibited, while the Discussion says it is unclear whether this reflects new growth or spared axons, so hindered axonal regrowth is overstated. (LLM, conf=0.88)
Experimental — accuracy not yet measuredmiR-21 is involved in astrocytic hypertrophy, glial scar progression, and astrocyte reactivity.
“this miRNA was demonstrated to be involved in astrocytic hypertrophy, glial scar progression and astrocyte reactivity [66,67].”
From Emerging Role of miR-21-5p in Neuron–Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer’s Disease (2022) · cites this paper as [66]
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References 54 · Cited by 220
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- Authors
- Bhalala, O. G., Pan, L., Sahni, V., McGuire, T. L., Gruner, K., Tourtellotte, W. G., & Kessler, J. A.
- Affiliations
- Northwestern University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-12-12
- Volume
- 32
- Issue
- 50
- Pages
- 17935-17947
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3538038
- OpenAlex
- W2011943543
- Cited by
- 220
- References
- 54
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 12 · 2023: 7 · 2022: 13 · 2021: 13 · 2020: 19 · 2019: 24 · 2018: 22 · 2017: 18 · 2016: 20 · 2015: 23 · 2014: 23 · 2013: 13
- FWCI
- 13.64
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Northwestern University
- National Institutes of Health (20778, R01 NS, K26OD010945, UL1TR000150, NS 20778)
- University of Illinois at Urbana-Champaign
- National Cancer Institute (P30CA060553)
- National Institute of Neurological Disorders and Stroke (R01NS020778, R01 NS 20778, K02NS046468, R01NS020013, R01 NS20013)
- National Institute of Biomedical Imaging and Bioengineering (R01EB003806)
- National Center for Research Resources (K26RR026099)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- miR-21, spinal cord injury, astrocyte activation, astrocyte hypertrophy, glial scar, axon regeneration, microRNA sponge, conditional overexpression, blood-brain barrier repair, therapeutic target
- MeSH terms
- Animals, Astrocytes, Disease Models, Animal, Humans, Immunohistochemistry, Mice, Transgenic, Spinal Cord Injuries, In Situ Hybridization, Reverse Transcriptase Polymerase Chain Reaction, MicroRNAs, Mice, HEK293 Cells, Real-Time Polymerase Chain Reaction
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