title: miR-21-5p alleviates leakage of injured brain microvascular endothelial barrier in vitro through suppressing inflammation and apoptosis.
abstract: Our recent researches have identified increased expression of miR-21-5p in rats brain following traumatic brain injury (TBI), which protected against blood-brain barrier (BBB) damage. To further study the mechanism underlying the role of miR-21-5p on alleviating BBB damage after TBI, we performed the scratch injury model on cultured brain microvascular endothelial cells (BMVECs), which formed the microvascular endothelial barrier - an integral part of the highly specialized BBB. The expression level of miR-21-5p in BMVECs was observed to be increased after scratch injury, and could be further up-regulated by transfecting miR-21-5p mimics. We found that up-regulation of miR-21-5p level in BMVECs can alleviate endothelial barrier damage and loss of tight junction proteins. To further investigate the mechanism of this protective effect, we evaluated the impact of miR-21-5p on inflammation and apoptosis in injured BMVECs. On one hand, miR-21-5p suppressed inflammation by regulating the expression of inflammatory cytokines and NF-kB signaling. On the other hand, miR-21-5p inhibited cellular apoptosis by regulating the expression of apoptosis factors and Akt signaling. In addition, we also detected the activity of Ang-1/Tie-2 axis (associated with BBB stabilization) in BMVECs after scratch injury, and found that miR-21-5p can promote its activation. Taken together, miR-21-5p alleviates leakage of injured brain microvascular endothelial barrier through suppressing inflammation and apoptosis, while impacting the activities of NF-kB, Akt and Ang-1/Tie-2 signaling. Thus, miR-21-5p could be a potential therapeutic target for interventions of BBB damage after TBI.
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China; Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin 300052, China; Laboratory of Neuro-Trauma, Tianjin Neurological Institute, Tianjin 300052, China.
authors.forename: Xintong
authors.initials: X
authors.lastname: Ge
authors.affiliation: Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China; Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin 300052, China; Laboratory of Neuro-Trauma, Tianjin Neurological Institute, Tianjin 300052, China; Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin 300052, China; Laboratory of Neuro-Trauma and Neurodegenerative Disorders, Tianjin Geriatrics Institute, Tianjin 300052, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Huang
authors.affiliation: Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China; Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin 300052, China; Laboratory of Neuro-Trauma, Tianjin Neurological Institute, Tianjin 300052, China; Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin 300052, China; Laboratory of Neuro-Trauma and Neurodegenerative Disorders, Tianjin Geriatrics Institute, Tianjin 300052, China.
authors.forename: Huabin
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin 300052, China; Laboratory of Neuro-Trauma and Neurodegenerative Disorders, Tianjin Geriatrics Institute, Tianjin 300052, China.
authors.forename: Zhaoli
authors.initials: Z
authors.lastname: Han
authors.affiliation: Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China; Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin 300052, China; Laboratory of Neuro-Trauma, Tianjin Neurological Institute, Tianjin 300052, China.
authors.forename: Fanglian
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin 300052, China; Laboratory of Neuro-Trauma and Neurodegenerative Disorders, Tianjin Geriatrics Institute, Tianjin 300052, China.
authors.forename: Shishuang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Zengguang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052, China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Kang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China; Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin 300052, China; Laboratory of Neuro-Trauma, Tianjin Neurological Institute, Tianjin 300052, China.
authors.forename: Rongcai
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Yue
authors.affiliation: Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin 300052, China; Laboratory of Neuro-Trauma and Neurodegenerative Disorders, Tianjin Geriatrics Institute, Tianjin 300052, China. Electronic address: leiping1974@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Lei
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052, China; Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin 300052, China; Laboratory of Neuro-Trauma, Tianjin Neurological Institute, Tianjin 300052, China. Electronic address: jianningzhang@hotmail.com.
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells; D005786:Gene Expression Regulation / Q000235:genetics; D007249:Inflammation / Q000235:genetics; D035683:MicroRNAs / Q000008:administration & dosage* / Q000378:metabolism; D055806:Microvessels; D061251:Primary Cell Culture; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D035683:MicroRNAs; C546082:mirn21 microRNA, rat
keywords: Blood-brain barrier; Brain microvascular endothelial barrier; MiR-21-5p; Traumatic brain injury