ArticleBiological research2024
Dorsal root ganglion-derived exosomes deteriorate neuropathic pain by activating microglia via the microRNA-16-5p/HECTD1/HSP90 axis.
Article in Biological research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Elucidation of key lactylation- and palmitoylation-related genes and their related mechanisms in the development of neuropathic pain.Medicine · 2026Article
- Exosomal Circ_STAT1-AS Delivery Induced by Dexmedetomidine Modulates Microglial Polarization to Alleviate Diabetic Peripheral Neuropathy by Inhibiting JAK/STAT1 Pathway.Diabetes & metabolism journal · 2026Article
- Exosomes: Roles and Therapeutic Potential in Pain.Biomedicines · 2026Review
- Exosome-mediated cell-cell communication: a new perspective on the mechanisms and therapeutic potential of diabetic microvascular complications.Frontiers in pharmacology · 2026Review
- CircRNA-Based Therapeutics: a New Frontier in Neuroinflammation Treatment.Molecular neurobiology · 2025Review
- Article
- MicroRNA-Based Delivery Systems for Chronic Neuropathic Pain Treatment in Dorsal Root Ganglion.Pharmaceutics · 2025Review
- Unveiling the Mechanisms of Pain in Endometriosis: Comprehensive Analysis of Inflammatory Sensitization and Therapeutic Potential.International journal of molecular sciences · 2025Review
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Authors and funding
6 authors.
Funding
Abstract
backgroundThe activated microglia have been reported as pillar factors in neuropathic pain (NP) pathology, but the molecules driving pain-inducible microglial activation require further exploration. In this study, we investigated the effect of dorsal root ganglion (DRG)-derived exosomes (Exo) on microglial activation and the related mechanism.
methodsA mouse model of NP was generated by spinal nerve ligation (SNL), and DRG-derived Exo were extracted. The effects of DRG-Exo on NP and microglial activation in SNL mice were evaluated using behavioral tests, HE staining, immunofluorescence, and western blot. Next, the differentially enriched microRNAs (miRNAs) in DRG-Exo-treated microglia were analyzed using microarrays. RT-qPCR, RNA pull-down, dual-luciferase reporter assay, and immunofluorescence were conducted to verify the binding relation between miR-16-5p and HECTD1. Finally, the effects of ubiquitination modification of HSP90 by HECTD1 on NP progression and microglial activation were investigated by Co-IP, western blot, immunofluorescence assays, and rescue experiments.
resultsDRG-Exo aggravated NP resulting from SNL in mice, promoted the activation of microglia in DRG, and increased neuroinflammation. miR-16-5p knockdown in DRG-Exo alleviated the stimulating effects of DRG-Exo on NP and microglial activation. DRG-Exo regulated the ubiquitination of HSP90 through the interaction between miR-16-5p and HECTD1. Ubiquitination alteration of HSP90 was involved in microglial activation during NP.
conclusionsmiR-16-5p shuttled by DRG-Exo regulated the ubiquitination of HSP90 by interacting with HECTD1, thereby contributing to the microglial activation in NP.
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