Transfer of miR-877–3p via extracellular vesicles derived from dental pulp stem cells attenuates neuronal apoptosis and facilitates early neurological functional recovery after cerebral ischemia–reperfusion injury through the Bclaf1/P53 signaling pathway

Yan Miao; Xin Liang; Jigang Chen; Hongyi Liu; Zilong He; Yongkai Qin; Aihua Liu; Ruxu Zhang

Pharmacological Research (Aug 2024)

Transfer of miR-877–3p via extracellular vesicles derived from dental pulp stem cells attenuates neuronal apoptosis and facilitates early neurological functional recovery after cerebral ischemia–reperfusion injury through the Bclaf1/P53 signaling pathway

Yan Miao,
Xin Liang,
Jigang Chen,
Hongyi Liu,
Zilong He,
Yongkai Qin,
Aihua Liu,
Ruxu Zhang

Affiliations

Yan Miao: Department of Neurology, The Third Xiangya Hospital, Central South University, 410013, China
Xin Liang: Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, 100038, China
Jigang Chen: Department of burn and plastic surgery, Beijing Children's Hospital, Capital Medical University, 100045, China
Hongyi Liu: Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, 100070, China; School of Biomedical Engineering, Capital Medical University, Beijing 100069, China
Zilong He: Department of Neurosurgery, The Third Xiangya Hospital, Central South University, 410013, China
Yongkai Qin: Department of Neurosurgery, The Third Xiangya Hospital, Central South University, 410013, China
Aihua Liu: Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, 100070, China; Department of Neurosurgery, The Third Xiangya Hospital, Central South University, 410013, China; Correspondence to: Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, No.119 South 4th Ring West Road, Fengtai District, Beijing 100070, China.
Ruxu Zhang: Department of Neurology, The Third Xiangya Hospital, Central South University, 410013, China; Correspondence to: Department of Neurology, The Third Xiangya Hospital, Central South University, No.138 Tongzipo Road, Yuelu District, Changsha, Hunan Province 410013, China.

Journal volume & issue: Vol. 206
p. 107266

Abstract

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Cerebral ischemia-reperfusion injury (I/RI) is one of the principal pathogenic factors in the poor prognosis of ischemic stroke, for which current therapeutic options to enhance neurological recovery are notably insufficient. Dental pulp stem cell-derived extracellular vesicles (DPSC-EVs) have promising prospects in stroke treatment and the specific underlying mechanisms have yet to be fully elucidated. The present study observed that DPSC-EVs ameliorated the degree of cerebral edema and infarct volume by reducing the apoptosis of neurons. Furthermore, the miRNA sequencing and functional enrichment analysis identified that miR-877–3p as a key component in DPSC-EVs, contributing to neuroprotection and anti-apoptotic effects. Following target prediction and dual-luciferase assay indicated that miR-877–3p interacted with Bcl-2-associated transcription factor (Bclaf1) to play a function. The miR-877–3p inhibitor or Bclaf1 overexpression reversed the neuroprotective effects of DPSC-EVs. The findings reveal a novel therapeutic pathway where miR-877–3p, transferred via DPSC-EVs, confers neuroprotection against cerebral I/RI, highlighting its potential in promoting neuronal survival and recovery post-ischemia.

Published in Pharmacological Research

ISSN: 1096-1186 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.sciencedirect.com/journal/pharmacological-research

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