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Increased miR-21-3p in Injured Brain Microvascular Endothelial Cells after Traumatic Brain Injury Aggravates Blood-Brain Barrier Damage by Promoting Cellular Apoptosis and Inflammation through Targeting MAT2B.

Publication ,  Journal Article
Ge, X; Li, W; Huang, S; Yin, Z; Yang, M; Han, Z; Han, Z; Chen, F; Wang, H; Lei, P; Zhang, J
Published in: J Neurotrauma
April 15, 2019

Our recent articles have reported that increased miR-21-5p in brain after traumatic brain injury (TBI) could improve the neurological outcome through alleviating blood-brain barrier (BBB) damage. miR-21-3p is another mature miRNA derived from pre-miR-21 after Dicer Procession other than miR-21-5p. Its roles in various diseases, such as tumors and myocardial disease, aroused great interest for research in recent years. To further explore the function and underlying mechanism of miR-21, especially miR-21-3p, in regulating the pathological development of BBB damage after TBI, we designed this research and focused on studying the impact of miR-21-3p on apoptosis and inflammation in brain microvascular endothelial cells (BMVECs), the major cellular component of BBB. We performed controlled cortical impact on mouse brain and employed the oxygen glucose deprivation/reoxygenation (OGD)-treated bEnd.3 cells injury model. We found that the miR-21-3p level in BMVECs from injured cerebral cortex of controlled cortical impact (CCI) mice and bEnd.3 cells with OGD treatment were both increased after injury. For in vitro experiments, downregulation on the miR-21-3p level by transfecting miR-21-3p antagomir in cultured cells alleviated OGD-induced BBB damage, characterized by decreased BBB leakage and increased expression of tight junction proteins. Besides, miR-21-3p antagomir could suppress cell death by anti-apoptosis and control inflammatory response by inhibiting the activity of NF-κB signaling. Using luciferase reporter assay and a MAT2B-silenced shRNA vector, we further proved that miR-21-3p exerted the above functions through targeting MAT2B. In addition, in vivo experiments also confirmed that intracerebroventricular infusion of miR-21-3p antagomir could alleviate BBB leakage after TBI. It reduced Evans Blue extravasation and promoted the expression of tight junction proteins, thus contributed to improve the neurological outcome of CCI mice. Taken together, increased miR-21-3p in BMVECs after TBI was bad for restoration of injured BBB. Downregulation on the miR-21-3p level in injured brain could be a promising therapeutic strategy for BBB damage after TBI.

Duke Scholars

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Published In

J Neurotrauma

DOI

EISSN

1557-9042

Publication Date

April 15, 2019

Volume

36

Issue

8

Start / End Page

1291 / 1305

Location

United States

Related Subject Headings

  • Neurology & Neurosurgery
  • MicroRNAs
  • Mice, Inbred C57BL
  • Mice
  • Methionine Adenosyltransferase
  • Male
  • Inflammation
  • Gene Expression Regulation
  • Endothelial Cells
  • Brain Injuries, Traumatic
 

Citation

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Ge, X., Li, W., Huang, S., Yin, Z., Yang, M., Han, Z., … Zhang, J. (2019). Increased miR-21-3p in Injured Brain Microvascular Endothelial Cells after Traumatic Brain Injury Aggravates Blood-Brain Barrier Damage by Promoting Cellular Apoptosis and Inflammation through Targeting MAT2B. J Neurotrauma, 36(8), 1291–1305. https://doi.org/10.1089/neu.2018.5728
Ge, Xintong, Wenzhu Li, Shan Huang, Zhenyu Yin, Mengchen Yang, Zhenying Han, Zhaoli Han, et al. “Increased miR-21-3p in Injured Brain Microvascular Endothelial Cells after Traumatic Brain Injury Aggravates Blood-Brain Barrier Damage by Promoting Cellular Apoptosis and Inflammation through Targeting MAT2B.J Neurotrauma 36, no. 8 (April 15, 2019): 1291–1305. https://doi.org/10.1089/neu.2018.5728.
Journal cover image

Published In

J Neurotrauma

DOI

EISSN

1557-9042

Publication Date

April 15, 2019

Volume

36

Issue

8

Start / End Page

1291 / 1305

Location

United States

Related Subject Headings

  • Neurology & Neurosurgery
  • MicroRNAs
  • Mice, Inbred C57BL
  • Mice
  • Methionine Adenosyltransferase
  • Male
  • Inflammation
  • Gene Expression Regulation
  • Endothelial Cells
  • Brain Injuries, Traumatic