The Signature of MicroRNA Dysregulation in Muscle Paralyzed by Spinal Cord Injury Includes Downregulation of MicroRNAs that Target Myostatin Signaling
Open accessAbstract
Spinal cord injury (SCI) results in muscle atrophy, reduced force generation and an oxidative-to-glycolytic fiber type shift. The mechanisms responsible for these alterations remain incompletely understood. To gain new insights regarding mechanisms involved in deterioration of muscle after SCI, global expression profiles of miRs in paralyzed gastrocnemius muscle were compared between sham-operated (Sham) and spinal cord-transected (SCI) rats. Ingenuity Pathways Analysis of the altered miRs identified signaling via insulin, IGF-1, integrins and TGF-β as being significantly enriched for target genes. By qPCR, miRs 23a, 23b, 27b, 145, and 206, were downregulated in skeletal muscle 56 days after SCI. Using FISH, miR-145, a miR not previously implicated in the function of skeletal muscle, was found to be localized to skeletal muscle fibers. One predicted target of miR-145 was Cited2, a transcriptional regulator that modulates signaling through NF-κB, Smad3 and other transcription factors. The 3' UTR of Cited2 mRNA contained a highly conserved miR-145 seed sequence. Luciferase reporter assays confirmed that miR-145 interacts with this seed sequence. However, Cited2 protein levels were similar between Sham and SCI groups, indicating a biochemical interaction that was not involved in the context of adaptations after SCI. Taken together, the findings indicate dysregulation of several highly expressed miRs in skeletal muscle after SCI and suggest that reduced expression of miR-23a, 145 and 206 may have roles in alteration in skeletal muscle mass and insulin responsiveness in muscle paralyzed by upper motor neuron injuries.
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The targets of miR-23a/b in the skeletal muscles of rats with spinal cord injury comprise TGF-β signal transduction.
“Their targets comprise TGF- β Signal transduction”
From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [138]
The Results section ('miRs altered after SCI by target multiple mRNA in TGF-ß signaling'; page unavailable) identifies confirmed or predicted TGF-β-signaling targets for miR-23a in the rat SCI study. It does not identify such targets for miR-23b, so the claim is supported for miR-23a but not for both miRNAs. (LLM, conf=0.86)
Experimental — accuracy not yet measuredmiR-23a/b are down-regulated in the skeletal muscles of rats with spinal cord injury.
“it was observed that miR-23a/b are down-regulated in the skeletal muscles of rats with spinal cord injury.”
From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [138]
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- Authors
- De Gasperi, R., Graham, Z. A., Harlow, L. M., Bauman, W. A., Qin, W., & Cardozo, C. P.
- Affiliations
- James J. Peters VA Medical Center (US)
- Corresponding author
- Cardozo, Christopher P.
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2016-12-01
- Volume
- 11
- Issue
- 12
- Pages
- e0166189
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5132212
- OpenAlex
- W2558182122
- Cited by
- 19
- References
- 65
- Citations by year
- 2024: 1 · 2023: 1 · 2021: 4 · 2019: 5 · 2018: 6 · 2017: 1 · 2016: 1
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- public-domain
- creativecommons.org/publicdomain/zero/1.0/ (vor)
- Locations
- PLoS ONE (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- VA Rehabilitation Research and Development Service (B9212C)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Keywords
- spinal cord injury, microRNA dysregulation, muscle atrophy, myostatin signaling, miR-145, miR-23a, miR-206, miR-23b, miR-27b, CITED2, insulin signaling, IGF-1 signaling, integrin signaling, TGF-beta signaling, gastrocnemius, upper motor neuron lesion, muscle fiber type shift, oxidative stress, miRNA target genes
- MeSH terms
- Animals, Gene Expression Regulation, Humans, Insulin, Male, Muscular Atrophy, RNA, Messenger, Spinal Cord Injuries, Signal Transduction, Muscle, Skeletal, MicroRNAs, Rats, Myostatin
About these checks
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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