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The lncRNA FAL1 protects against hypoxia-reoxygenation- induced brain endothelial damages through regulating PAK1

  • Mingqing Gao
  • Jieting Fu
  • Yanqiang WangEmail author
Article
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Abstract

Dysregulation of cerebral microvascular endothelial cells plays an important role in the pathogenesis of stroke. However, the underlying mechanisms still need to be elucidated. In the current study, we found that the long non-coding RNA (lncRNA) FAL1 was significantly reduced in response to oxygen-glucose deprivation and reoxygenation (OGD/R) stimulation in human primary brain microvascular endothelial cells (HBMVECs). Interestingly, overexpression of FAL1 ameliorated OGD/R-induced oxidative stress by reducing the production of reactive oxygen species (ROS) and increasing the level of reduced glutathione (GSH). Also, overexpression of FAL1 suppressed OGD/R-induced secretions of interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and high mobility group box-1 (HMGB-1). We then found that OGD/R-induced reduction of cell viability and release of lactate dehydrogenase (LDH) were prevented by overexpression of FAL1. Additionally, exposure to OGD/R significantly reduced the phosphorylated levels of PAK1 and AKT as well as the total level of proliferating cell nuclear antigen (PCNA), which was restored by overexpression of FAL1. Importantly, overexpression of FAL1 restored OGD/R-induced reduction in the expression of endothelial nitric oxide synthase (eNOS) and the subsequent release of nitric oxide (NO). Our results implicate that FAL1 might be involved in the process of brain endothelial cell damage.

Keywords

Stroke Oxygen-glucose deprivation and reoxygenation lncRNA FAL1 Cerebral microvascular endothelial cells 

Notes

Acknowledgements

This work was supported by the Shandong Provincial Nature Fund Joint Special Fund Project (ZR2018LH006) and the Key Research and Development Program of Shandong Province (2015GSF118146).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest that need to be disclosed.

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© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Department of NeurosurgeryThe Affiliated Hospital of Wei fang Medical UniversityWeifangChina
  2. 2.Department of HematologyThe Affiliated Hospital of Wei fang Medical UniversityShandongChina
  3. 3.Department of NeurologyThe Affiliated Hospital of Wei fang Medical UniversityShandongChina

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