ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
Astrocyte-derived exosomal lncRNA 4933431K23Rik modulates microglial phenotype and improves post-traumatic recovery via SMAD7 regulation.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
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- Caspase-1 in cancer and inflammatory diseases: a potential therapeutic target.Apoptosis : an international journal on programmed cell death · 2026Review
- Source-Specific Extracellular Vesicle Functions and Engineering Strategies for Chronic Pain Management: A Comprehensive Review.International journal of nanomedicine · 2026Review
- Protective role of miR-712-3p in heatstroke-induced brain injury: involvement of neuronal lysosomal function and association with astrocytic exosome-enriched preparations.Frontiers in pharmacology · 2026Article
- The role of non-coding RNAs in the pathogenesis of migraine: from molecular insights to potential biomarkers.Frontiers in neurology · 2026Review
- Exosome-Based Diagnostics and Cell-Free Therapeutics for Traumatic Brain Injury: From Mechanisms to Bedside.International journal of nanomedicine · 2026Review
- Unveiling the Role of LncRNA in Sepsis-Associated Encephalopathy.Current medical science · 2025Review
- Post-translational modifications regulating microglial inflammation in central nervous system disorders: a review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Orlistat Confers Neuroprotection in Traumatic Brain Injury by Modulating Microglial Lipid Metabolism.Cells · 2025Article
- Unveiling the predictive power of biomarkers in traumatic brain injury: A narrative review focused on clinical outcomes.Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia · 2025Review
- Role of extracellular vesicle-carried ncRNAs in the interactive 'dialogue' within the brain and beyond: emerging theranostic epigenetic modifiers in brain-derived nanoplatforms.Translational neurodegeneration · 2025Review
- Impact of Microglia-Derived Extracellular Vesicles on Resident Central Nervous System Cell Populations After Acute Brain Injury Under Various External Stimuli Conditions.Molecular neurobiology · 2025Review
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- Astrocyte-derived extracellular vesicular NFIA mediates obesity-associated cognitive impairment.Journal of neuroinflammation · 2025Article
- Precision exosome engineering for neurological therapeutics: molecular mechanisms and targeted strategies.Molecular biology reports · 2025Review
- Harnessing the Potential of Exosomes in Therapeutic Interventions for Brain Disorders.International journal of molecular sciences · 2025Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Astrocyte-microglial interaction plays a crucial role in brain injury-associated neuroinflammation. Our previous data illustrated that astrocytes secrete microRNA, leading to anti-inflammatory effects on microglia. Long non-coding RNAs participate in neuroinflammation regulation after traumatic brain injury. However, the effect of astrocytes on microglial phenotype via long non-coding RNAs and the underlying molecular mechanisms remain elusive. We used long non-coding RNA sequencing on murine astrocytes and found that exosomal long non-coding RNA 4933431K23Rik attenuated traumatic brain injury-induced microglial activation in vitro and in vivo and ameliorated cognitive function deficiency. Furthermore, microRNA and messenger RNA sequencing together with binding prediction illustrated that exosomal long non-coding RNA 4933431K23Rik up-regulates E2F7 and TFAP2C expression by sponging miR-10a-5p. Additionally, E2F7 and TFAP2C, as transcription factors, regulated microglial Smad7 expression. Using Cx3cr1-Smad7 overexpression of adeno-associated virus, microglia specifically overexpressed Smad7 in the attenuation of neuroinflammation, resulting in less cognitive deficiency after traumatic brain injury. Mechanically, overexpressed Smad7 physically binds to IκBα and inhibits its ubiquitination, preventing NF-κB signaling activation. The Smad7 activator asiaticoside alleviates neuroinflammation and protects neuronal function in traumatic brain injury mice. This study revealed that an exosomal long non-coding RNA from astrocytes attenuates microglial activation after traumatic brain injury by up-regulating Smad7, providing a potential therapeutic target.
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