ArticleExperimental neurology2016
Overexpression of the monocyte chemokine CCL2 in dorsal root ganglion neurons causes a conditioning-like increase in neurite outgrowth and does so via a STAT3 dependent mechanism.
Article in Experimental neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 85 citations in OpenAlex.
- Single-cell and single-nucleus transcriptomics of the dorsal root ganglion in neuropathic pain: cell-state remodeling and translational prospects.Journal of translational medicine · 2026Review
- Aging-Related Changes in the Injury Response of the Peripheral Nervous System.Neuroscience bulletin · 2026Review
- Revisiting the Peripheral Nerve Injury and Regeneration.Neuromolecular medicine · 2026Review
- Engineered CCR2 positive macrophages coordinate immunoregulation with neural regeneration and matrix remodeling after spinal cord injury.Theranostics · 2026Article
- The dual roles of chemokines in peripheral nerve injury and repair.Inflammation and regeneration · 2025Review
- Transcriptomic Analysis of the Rat Dorsal Root Ganglion After Fracture.Molecular neurobiology · 2024Article
- Neuronal chemokines: new insights into neuronal communication after injury.Neural regeneration research · 2023Article
- Switching Rat Resident Macrophages from M1 to M2 Phenotype by Iba1 Silencing Has Analgesic Effects in SNL-Induced Neuropathic Pain.International journal of molecular sciences · 2023Article
- Transcriptomic analysis of diabetic kidney disease and neuropathy in mouse models of type 1 and type 2 diabetes.Disease models & mechanisms · 2023Article
- The significance of M1 macrophage should be highlighted in peripheral nerve regeneration.Histology and histopathology · 2023Review
- Article
- Self-renewing macrophages in dorsal root ganglia contribute to promote nerve regeneration.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Peripheral CCL2 induces inflammatory pain via regulation ofFrontiers in molecular neuroscience · 2023Article
- Neurexin-β Mediates the Synaptogenic Activity of Amyloid Precursor Protein.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Autoimmunity, cancer and COVID-19 abnormally activate wound healing pathways: critical role of inflammation.Histochemistry and cell biology · 2022Review
- The Yin/Yang Balance of Communication between Sensory Neurons and Macrophages in Traumatic Peripheral Neuropathic Pain.International journal of molecular sciences · 2022Review
- Clinically relevant small-molecule promotes nerve repair and visual function recovery.NPJ Regenerative medicine · 2022Article
- Boosting the peripheral immune response in the skeletal muscles improved motor function in ALS transgenic mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- The primary macrophage chemokine, CCL2, is not necessary after a peripheral nerve injury for macrophage recruitment and activation or for conditioning lesion enhanced peripheral regeneration.Journal of neuroinflammation · 2022Article
- Mesenchymal Stem Cells in the Treatment of Human Spinal Cord Injury: The Effect on Individual Values of pNF-H, GFAP, S100 Proteins and Selected Growth Factors, Cytokines and Chemokines.Current issues in molecular biology · 2022Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Neuroinflammation plays a critical role in the regeneration of peripheral nerves following axotomy. An injury to the sciatic nerve leads to significant macrophage accumulation in the L5 DRG, an effect not seen when the dorsal root is injured. We recently demonstrated that this accumulation around axotomized cell bodies is necessary for a peripheral conditioning lesion response to occur. Here we asked whether overexpression of the monocyte chemokine CCL2 specifically in DRG neurons of uninjured mice is sufficient to cause macrophage accumulation and to enhance regeneration or whether other injury-derived signals are required. AAV5-EF1α-CCL2 was injected intrathecally, and this injection led to a time-dependent increase in CCL2 mRNA expression and macrophage accumulation in L5 DRG, with a maximal response at 3 weeks post-injection. These changes led to a conditioning-like increase in neurite outgrowth in DRG explant and dissociated cell cultures. This increase in regeneration was dependent upon CCL2 acting through its primary receptor CCR2. When CCL2 was overexpressed in CCR2-/- mice, macrophage accumulation and enhanced regeneration were not observed. To address the mechanism by which CCL2 overexpression enhances regeneration, we tested for elevated expression of regeneration-associated genes in these animals. Surprisingly, we found that CCL2 overexpression led to a selective increase in LIF mRNA and neuronal phosphorylated STAT3 (pSTAT3) in L5 DRGs, with no change in expression seen in other RAGs such as GAP-43. Blockade of STAT3 phosphorylation by each of two different inhibitors prevented the increase in neurite outgrowth. Thus, CCL2 overexpression is sufficient to induce macrophage accumulation in uninjured L5 DRGs and increase the regenerative capacity of DRG neurons via a STAT3-dependent mechanism.
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