STAT3 is a Critical Regulator of Astrogliosis and Scar Formation after Spinal Cord Injury
Open accessAbstract
Signaling mechanisms that regulate astrocyte reactivity and scar formation after spinal cord injury (SCI) are not well defined. We used the Cre recombinase (Cre)- loxP system under regulation of the mouse glial fibrillary acidic protein (GFAP) promoter to conditionally delete the cytokine and growth factor signal transducer, signal transducer and activator of transcription 3 (STAT3), from astrocytes. After SCI in GFAP-Cre reporter mice, >99% of spinal cord cells that exhibited Cre activity as detected by reporter protein expression were GFAP-expressing astrocytes. Conditional deletion (or knock-out) of STAT3 (STAT3-CKO) from astrocytes in GFAP-Cre- loxP mice was confirmed in vivo and in vitro . In uninjured adult STAT3-CKO mice, astrocytes appeared morphologically similar to those in STAT3+/+ mice except for a partially reduced expression of GFAP. In STAT3+/+ mice, phosphorylated STAT3 (pSTAT3) was not detectable in astrocytes in uninjured spinal cord, and pSTAT3 was markedly upregulated after SCI in astrocytes and other cell types near the injury. Mice with STAT3-CKO from astrocytes exhibited attenuated upregulation of GFAP, failure of astrocyte hypertrophy, and pronounced disruption of astroglial scar formation after SCI. These changes were associated with increased spread of inflammation, increased lesion volume and partially attenuated motor recovery over the first 28 d after SCI. These findings indicate that STAT3 signaling is a critical regulator of certain aspects of reactive astrogliosis and provide additional evidence that scar-forming astrocytes restrict the spread of inflammatory cells after SCI.
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Activation of STAT3-dependent transcription is beneficial in neonatal white matter injury, traumatic brain injury, spinal cord injury, and motor neuron injury, but detrimental in AD models.
“For example, activation of STAT3-dependent transcription is beneficial in neonatal white matter injury47, traumatic brain injury30, spinal cord injury48,49, and motor neuron injury50, but detrimental in AD models42,43.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [49]
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- Authors
- Herrmann, J. E., Imura, T., Song, B., Qi, J., Ao, Y., Nguyen, T. K., Korsak, R. A., Takeda, K., Akira, S., & Sofroniew, M. V.
- Affiliations
- University of California, Los Angeles (US)
- Kyushu University (JP)
- Research Institute for Microbial Diseases, The University of Osaka (JP)
- Corresponding author
- Sofroniew, Michael V.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-07-09
- Volume
- 28
- Issue
- 28
- Pages
- 7231-7243
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2583788
- OpenAlex
- W2121860798
- Cited by
- 958
- References
- 5
- Citations by year
- 2026: 46 · 2025: 50 · 2024: 59 · 2023: 54 · 2022: 53 · 2021: 81 · 2020: 63 · 2019: 61 · 2018: 54 · 2017: 60 · 2016: 55 · 2015: 55 · 2014: 72 · 2013: 43 · 2012: 49
- FWCI
- 24.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- National Institutes of Health (NS057624)
- Centers for Disease Control and Prevention (ND042693)
- National Institute of Neurological Disorders and Stroke (NS057624, R21NS042693, R01NS047386, R01NS057624)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- STAT3, spinal cord injury, astrocyte activation, glial fibrillary acidic protein, conditional knockout, astrocyte hypertrophy, lesion volume, motor recovery, cytokine signaling
- MeSH terms
- Analysis of Variance, Animals, Animals, Newborn, Astrocytes, Behavior, Animal, Cell Count, Cells, Cultured, Cicatrix, Gene Expression Regulation, Gliosis, Mice, Inbred C57BL, Spinal Cord Injuries, Time Factors, Leukocyte Common Antigens, Mice, Knockout, Green Fluorescent Proteins, STAT3 Transcription Factor, Mice
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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