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Altered long non-coding RNA transcriptomic profiles in brain microvascular endothelium after cerebral ischemia
1Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Experimental Neurology
|January 10, 2016
Summary
This study identifies novel long non-coding RNAs (lncRNAs) in brain endothelial cells that change expression after stroke conditions. These lncRNAs may play key roles in cerebrovascular dysfunction and stroke pathophysiology.
Area of Science:
- Neuroscience
- Molecular Biology
- Genomics
Background:
- The brain endothelium is a critical therapeutic target for ischemic stroke.
- MicroRNAs are known regulators of cerebral vasculature, but other non-coding RNAs remain uncharacterized in stroke.
- The role of long non-coding RNAs (lncRNAs) in cerebrovascular endothelial cells during stroke is unknown.
Purpose of the Study:
- To profile long non-coding RNA (lncRNA) expression in brain endothelial cells under ischemic conditions.
- To identify specific lncRNAs that are altered in response to oxygen-glucose deprivation (OGD) and their potential role in stroke pathophysiology.
Main Methods:
- RNA sequencing (RNA-seq) was used to analyze lncRNA expression in primary brain microvascular endothelial cells (BMECs) after OGD.
- Quantitative real-time PCR (qRT-PCR) was employed to validate lncRNA expression changes in vitro and in vivo mouse models (transient middle cerebral artery occlusion - MCAO).
- Bioinformatic promoter analysis was performed to predict transcriptional regulation of identified lncRNAs.
Main Results:
- Out of 10,677 analyzed lncRNAs, 362 showed significant expression changes after 16h OGD in BMECs.
- 147 lncRNAs were upregulated and 70 were downregulated more than 2-fold.
- Key upregulated lncRNAs included Snhg12, Malat1, and lnc-OGD 1006; downregulated lncRNAs included 281008D09Rik, Peg13, and lnc-OGD 3916.
- Expression alterations were confirmed in OGD-treated BMECs and MCAO-subjected mouse cerebral microvessels.
- Bioinformatic analysis suggested potential transcriptional regulation of these lncRNAs.
Conclusions:
- This study presents the first identification of OGD-responsive lncRNAs in brain endothelial cells.
- These novel lncRNAs may have pathological roles in endothelial responses to ischemic stimuli.
- Endothelial-selective lncRNAs represent a potential new class of master regulators in cerebrovascular endothelial pathologies post-stroke.
Keywords:
Brain microvascular endothelial cellsIschemic strokeLong non-coding RNAsOxygen–glucose deprivationRNA sequencingTranscriptome
