miR-223 accelerates lipid droplets clearance in microglia following spinal cord injury by upregulating ABCA1
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Abstract
Background: Spinal cord injury (SCI) is characterized by extensive demyelination and inflammatory responses. Facilitating the clearance of lipid droplets (LDs) within microglia contributes to creating a microenvironment that favors neural recovery and provides essential materials for subsequent remyelination. Therefore, investigating MicroRNAs (miRNAs) that regulate lipid homeostasis after SCI and elucidating their potential mechanisms in promoting LDs clearance in microglia have become focal points of SCI research. Methods: We established a subacute C5 hemicontusion SCI model in mice and performed transcriptomic sequencing on the injury epicenter to identify differentially expressed genes and associated pathways. Confocal imaging was employed to observe LDs accumulation. Multi-omics analyses were conducted to identify differentially expressed mRNA and miRNA post-SCI. Pathway enrichment analysis and protein-protein interaction network construction were performed using bioinformatics methods, revealing miR-223- Abca1 as a crucial miRNA-mRNA pair in lipid metabolism regulation. BV2 microglia cell lines overexpressing miR-223 were engineered, and immunofluorescence staining, western blot, and other techniques were employed to assess LDs accumulation, relevant targets, and inflammatory factor expression, confirming its role in regulating lipid homeostasis in microglia. Results: Histopathological results of our hemicontusion SCI model confirmed LDs aggregation at the injury epicenter, predominantly within microglia. Our transcriptomic analysis during the subacute phase of SCI in mice implicated ATP-binding cassette transporter A1 ( Abca1 ) as a pivotal gene in lipid homeostasis, cholesterol efflux and microglial activation. Integrative mRNA-miRNA multi-omics analysis highlighted the crucial role of miR-223 in the neuroinflammation process following SCI, potentially through the regulation of lipid metabolism via Abca1 . In vitro experiments using BV2 cells overexpressing miR-223 demonstrated that elevated levels of miR-223 enhance ABCA1 expression in myelin debris and LPS-induced BV2 cells. This promotes myelin debris degradation and LDs clearance, and induces a shift toward an anti-inflammatory M2 phenotype. Conclusions: In summary, our study unveils the critical regulatory role of miR-223 in lipid homeostasis following SCI. The mechanism by which this occurs involves the upregulation of ABCA1 expression, which facilitates LDs clearance and myelin debris degradation, consequently alleviating the lipid burden, and inhibiting inflammatory polarization of microglia. These findings suggest that strategies to enhance miR-223 expression and target ABCA1, thereby augmenting LDs clearance, may emerge as appealing new clinical targets for SCI treatment.
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Self-citationTartaglia, M., Ioni, A., Luca, M. D., Vilardo, L., D’Agnano, I., Conte, A., Limatola, C., & Catalano, M. (2026) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2026.1864654
- Authors
- Ou, Z., Cheng, Y., Ma, H., Chen, K., Lin, Q., Chen, J., Guo, R., Huang, Z., Cheng, Q., Alaeiilkhchi, N., Zhu, Q., Huang, Z., & Jiang, H.
- Affiliations
- Nanfang Hospital (CN)
- Southern Medical University (CN)
- University of British Columbia (CA)
- Corresponding author
- Huang, Zhiping
- Huang, Zucheng
- Jiang, Hui
- ORCID
- Venue
- Journal of Translational Medicine
- Published
- 2024-07-15
- Volume
- 22
- Issue
- 1
- Pages
- 659-659
- ISSN
- 1479-5876 (ISSN-L)
- PMC
- PMC11247820
- OpenAlex
- W4400659205
- Semantic Scholar
- 3a078d8ba7ba24c88dc33c2250b3242db4726328
- Cited by
- 23
- References
- 68
- Citations by year
- 2026: 14 · 2025: 9
- FWCI
- 5.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Translational Medicine (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Natural Science Foundation of China (81972064, 81902217)
- Natural Science Foundation of Guangdong Province (2023A1515010565, 2020A1515011415)
- 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 › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- miR-223, ABCA1, spinal cord injury, lipid droplets, microglia, lipid homeostasis, neuroinflammation, microglial M2 polarization, cholesterol efflux, remyelination, miRNA-mRNA regulatory network, BV-2 cells, lipopolysaccharide-induced inflammation, multi-omics
- MeSH terms
- Animals, Cell Line, Male, Mice, Inbred C57BL, Spinal Cord Injuries, Up-Regulation, Microglia, MicroRNAs, Lipid Metabolism, Mice, ATP Binding Cassette Transporter 1, Lipid Droplets
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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