ArticleCNS neuroscience & therapeutics2025
H4K12 Lactylation Activated-Spp1 in Reprogrammed Microglia Improves Functional Recovery After Spinal Cord Injury.
Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- NOTCH-mediated glial CXCL9:SPP1 polarization by GSK3β exacerbates postnatal enteric nervous system dysfunction in Hirschsprung disease.Journal of gastroenterology · 2026Article
- Unveiling a unique microglial phenotype promoting oxidation in the iBRB: insights from single-cell transcriptomics in the NPDR rat model.Cell & bioscience · 2026Article
- A Novel Approach to Neuropathic Pain Treatment: Lactylation Targeting Microglia.Molecular neurobiology · 2026Review
- Crosstalk between SPP1+ macrophages and ITGA5+ fibroblasts promotes hepatocellular carcinoma metastasis.Hepatology communications · 2026Article
- Lactylation and macrophage polarization from a clinical perspective: pathological mechanisms and therapeutic potential.Frontiers in immunology · 2026Review
- Gut-brain axis mechanisms of remote brain dysfunction after traumatic spinal cord injury: immune inflammation, the vagus nerve, and neuroendocrine pathways.Frontiers in cellular neuroscience · 2026Review
- Lactylation at the crossroads of metabolism and epigenetics in neuroinflammation.Frontiers in immunology · 2026Review
- Beyond Fuel: Exercise-Induced Lactate as a Metabolic-Epigenetic Regulator in Central Nervous System Health and Disease.Biomolecules · 2025Review
- Lactylation Dynamics and Its Regulatory Roles in Orthopedic Pathologies: A Research Update.Journal of proteome research · 2025Review
- Exploring the mechanisms of mutual influence between lactylation and macrophage polarization in the context of disease.Clinical and translational medicine · 2025Review
- Comments on "H4K12 Lactylation-Activated Spp1 in Reprogrammed Microglia Improves Functional Recovery After Spinal Cord Injury".CNS neuroscience & therapeutics · 2025Article
- Apigenin Suppresses NLRP3 Inflammasome Activation and Pyroptosis and Promotes Functional Recovery by Promoting Mitophagy in Experimental Spinal Cord Injured Rats.Journal of inflammation research · 2025Article
- Single-Cell RNA Sequencing Reveals Microglial Heterogeneity and Functional States After Cerebral Ischemia-Reperfusion Injury.Journal of inflammation research · 2025Article
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Authors and funding
9 authors.
Funding
Abstract
backgroundSpinal cord injury (SCI) is a severe condition leading to significant disability and high mortality. The role of the secreted phosphoprotein 1 (SPP1) signaling pathway in SCI, which is quickly activated after injury, is critical for intercellular communication but remains poorly understood.
aimsThis study aimed to explore the function and regulatory mechanisms of the SPP1 signaling pathway in SCI and investigate its potential as a therapeutic target for improving functional recovery after injury. MATERIALS AND
methodsSingle-cell RNA sequencing (scRNA-seq) was employed to identify ligands and receptors of the SPP1 signaling pathway, particularly in microglia/macrophages. Recombinant SPP1 (rSPP1) was used in vitro and in vivo to assess its effects on neuronal maturation, mitochondrial energy in axons, and functional recovery after SCI. Pseudotime analysis was conducted to examine the role of Spp1 in microglial activation and proliferation. DNA-pulldown and in vitro experiments were performed to investigate the upstream regulatory proteins of Spp1.
resultsThe SPP1 signaling pathway is primarily localized in microglia after SCI, with rSPP1 promoting neuronal maturation and enhancing mitochondrial function in axons. Injection of rSPP1 into the injured spinal cord resulted in significant improvement in functional recovery. Pseudotime analysis indicated that Spp1 is involved in the activation and proliferation of microglia. Histone H4 lysine 12 lactylation (H4K12la) was found to promote the transcription of Spp1 in reprogrammed microglia postinjury. DISCUSSION: Our findings reveal a novel regulatory mechanism involving Spp1 in SCI, particularly its role in microglial activation, mitochondrial function, and glycolytic reprogramming. This new insight provides a deeper understanding of its contribution to the injury response.
conclusionThis study uncovers a previously unreported mechanism of Spp1 in SCI, offering a potential therapeutic target for SCI.
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