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Silencing microRNA-143 protects the integrity of the blood-brain barrier: implications for methamphetamine abuse

Ying Bai1, Yuan Zhang1, Jun Hua2

  • 1Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu, China.

Scientific Reports
|October 22, 2016
PubMed

Insights

Silencing microRNA-143 (miR-143) protects blood-brain barrier (BBB) integrity against methamphetamine-induced damage by increasing tight junction proteins. This suggests miR-143 silencing as a potential therapy for BBB vascular dysfunction.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • The role of microRNA-143 (miR-143) in maintaining blood-brain barrier (BBB) integrity is not well understood.
  • The BBB is crucial for brain function and its disruption is implicated in various neurological disorders.

Purpose of the Study:

  • To investigate the role of miR-143 in BBB integrity and its potential as a therapeutic target.
  • To elucidate the molecular mechanisms by which miR-143 affects BBB permeability.

Main Methods:

  • Utilized a genetic animal model and lentivirus to silence miR-143.
  • Assessed BBB permeability and tight junction protein (TJP) expression in human brain endothelial cells.
  • Investigated the involvement of p53, NF-κB, MAPK, PI3K/Akt, and STAT3 pathways.

Main Results:

  • Silencing miR-143 prevented methamphetamine-induced BBB damage.
  • miR-143 directly targets p53 unregulated modulator of apoptosis (PUMA), increasing endothelial permeability and decreasing TJPs.
  • Silencing miR-143 restored TJP expression and protected BBB integrity.
  • PUMA overexpression enhanced TJP expression via NF-κB and p53 pathways.
  • Methamphetamine up-regulated miR-143 through sigma-1 receptor and downstream signaling pathways (MAPK, PI3K/Akt, STAT3).

Conclusions:

  • miR-143 plays a significant role in regulating BBB integrity.
  • Targeting miR-143 offers a novel therapeutic strategy for mitigating BBB damage and associated vascular dysfunction.

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