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Med Sci Monit. 2019 Mar 12;25:1871-1885. doi: 10.12659/MSM.915727.

Exosomes from MiR-21-5p-Increased Neurons Play a Role in Neuroprotection by Suppressing Rab11a-Mediated Neuronal Autophagy In Vitro After Traumatic Brain Injury.

Li D1,2, Huang S1,2, Zhu J3, Hu T1,2, Han Z1,2, Zhang S1,2, Zhao J1,2, Chen F4,5, Lei P1,2.

Author information

1
Laboratory of Neuro-Trauma and Neurodegenerative Disorders, Tianjin Geriatrics Institute, Tianjin Medical University General Hospital, Tianjin, China (mainland).
2
Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China (mainland).
3
Department of Ultrasound Diagnosis and Treatment, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China (mainland).
4
Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China (mainland).
5
Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China (mainland).

Abstract

BACKGROUND Traumatic brain injury (TBI) produces a series of pathological processes. Recent studies have indicated that autophagy pathway is persistently activated after TBI, which may lead to deterioration of nerve injury. Our preliminary work found miR-21-5p was upregulated in both in vivo and in vitro TBI models. MicroRNAs (miRNAs) could be loaded into exosomes to perform cell-to-cell interactions. This research aimed to evaluate the therapeutic effect of neuron-derived exosomes enriched with miR-21-5p on the TBI in vitro and to further explore the possible mechanisms. MATERIAL AND METHODS Brain extracts harvested from an rTBI mouse model were added to cultured HT-22 neurons to imitate the microenvironment of injured brain on in vitro cultured cells. Ultracentrifugation was performed to isolate exosomes. Transmission electron microscopy and Nano sight technology were used to examine exosomes. An in vitro model of TBI was established to study the effect of exosomal miR-21-5p on nerve injury and on neuronal autophagy regulation. RESULTS The expression of miR-21-5p was increased in exosomes derived from HT-22 neurons after treatment with rTBI mouse brain extracts. Autophagy was activated in HT-22 neurons after scratch injury. Exosomal miR-21-5p produced a protective effect by suppressing autophagy in a TBI model in vitro. MiR-21-5p could directly target the Rab11a 3'UTR region to reduce its translation and further suppressed Rab11a-mediated neuronal autophagy. CONCLUSIONS The levels of miR-21-5p in neuronal exosomes increased from the acute to the chronic phase of TBI. Neuronal exosomes enriched with miR-21-5p can inhibit the activity of neuronal autophagy by targeting Rab11a, thus attenuating trauma-induced, autophagy-mediated nerve injury in vitro.

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