ArticleCellular and molecular life sciences : CMLS2022
IL4 stimulated macrophages promote axon regeneration after peripheral nerve injury by secreting uPA to stimulate uPAR upregulated in injured axons.
Article in Cellular and molecular life sciences : CMLS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 11 citations in OpenAlex.
- uPAR exhibits age- and region-dependent expression in the brains of mice with Alzheimer's disease-like pathology.Brain research · 2026Article
- Activating Transcription Factor 3 in Pain: A Molecular Regulator and Emerging Biomarker.Genes · 2026Review
- Mechanisms, Biomarkers, and Therapeutic Interventions of Neuroplasticity After Ischemic Stroke-A Scoping Review.Brain sciences · 2026Review
- SARM1 is required for macrophage immunophenotype switching that is essential for nerve repair.bioRxiv : the preprint server for biology · 2026Article
- A sequential multimodal framework for spinal cord regeneration.Frontiers in cellular neuroscience · 2026Article
- Differentiated mesenchymal stem cells-derived exosomes immobilized in decellularized sciatic nerve hydrogels for peripheral nerve repair.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Advancing neural regeneration via adaptable hydrogels: Enriched with MgBioactive materials · 2024Article
- M2 macrophage-derived cathepsin S promotes peripheral nerve regeneration via fibroblast-Schwann cell-signaling relay.Journal of neuroinflammation · 2023Article
- Ultrasound therapy for a week promotes regeneration and reduces pro-inflammatory macrophages in a rat sciatic nerve autograft model.Scientific reports · 2023Article
- Metformin induces M2 polarization via AMPK/PGC-1α/PPAR-γ pathway to improve peripheral nerve regeneration.American journal of translational research · 2023Article
- Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Accumulating evidences suggest that M2 macrophages are involved with repair processes in the nervous system. However, whether M2 macrophages can promote axon regeneration by directly stimulating axons nor its precise molecular mechanism remains elusive. Here, the current study demonstrated that typical M2 macrophages, which were generated by IL4 simulation, had the capacity to stimulate axonal growth by their direct effect on axons and that the graft of IL4 stimulated macrophages into the region of Wallerian degeneration enhanced axon regeneration and improved functional recovery after PNI. Importantly, uPA (urokinase plasminogen activator)-uPA receptor (uPAR) was identified as the central axis underlying the axon regeneration effect of IL4 stimulated macrophages. IL4 stimulated macrophages secreted uPA, and its inhibition abolished their axon regeneration effect. Injured but not intact axons expressed uPAR to be sensitive to uPA. These results unveil a cellular and molecular mechanism underlying the macrophage related axon regeneration and provide a basis of a novel therapy for PNI.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.