期刊
SCIENTIFIC REPORTS
卷 10, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41598-020-59997-y
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资金
- AHA [16SDG31170008]
- NSF [1008182 R]
- WVCTSI [NIH/NIGMS U54GM104942]
- WVU Bridge Funding Grant
- WVU SURI Program
- NIH [P30 RR032138/GM103488, GM103434, R01 HL-128485, 1P20GM121322-01A1, P20 GM109098]
- Community Foundation for the Ohio Valley Whipkey Trust
- [P20GM103434]
Blood-brain barrier (BBB) dysfunction occurs in cerebrovascular diseases and neurodegenerative disorders such as stroke. Opening of the BBB during a stroke has a negative impact on acute outcomes. We have recently demonstrated that miR-34a regulates the BBB by targeting cytochrome c (CYC) in vitro. To investigate the role of miR-34a in a stroke, we purified primary cerebrovascular endothelial cells (pCECs) from mouse brains following 1 h transient middle cerebral artery occlusion (tMCAO) and measured real-time PCR to detect miR-34a levels. We demonstrate that the miR-34a levels are elevated in pCECs from tMCAO mice at the time point of BBB opening following 1 h tMCAO and reperfusion. Interestingly, knockout of miR-34a significantly reduces BBB permeability, alleviates disruption of tight junctions, and improves stroke outcomes compared to wild-type (WT) controls. CYC is decreased in the ischemic hemispheres and pCECs from WT but not in miR-34a(-/-) mice following stroke reperfusion. We further confirmed CYC is a target of miR-34a by a dural luciferase reporter gene assay in vitro. Our study provides the first description of miR-34a affecting stroke outcomes and may lead to discovery of new mechanisms and treatments for cerebrovascular and neurodegenerative diseases such as stroke.
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