MicroRNA-15a/16-1 antagomir ameliorates ischemic brain injury in experimental stroke
| Autor: | Ping Sun, Ke-Jie Yin, Yejie Shi, Sulaiman H Hassan, Kai Liu, R. Anne Stetler, Xinxin Yang, Jun Chen, Xuelian Tang |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Pathology Inflammation Ischemic brain injury Article Brain Ischemia Brain ischemia 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Internal medicine microRNA medicine Animals In patient Antagomir Stroke Advanced and Specialized Nursing Mice Knockout business.industry Antagomirs Infarction Middle Cerebral Artery medicine.disease Mice Inbred C57BL Disease Models Animal MicroRNAs 030104 developmental biology chemistry Potential biomarkers Cardiology Neurology (clinical) medicine.symptom Cardiology and Cardiovascular Medicine business 030217 neurology & neurosurgery |
| Popis: | Background and Purpose— Dysregulation of the miR-15a/16-1 cluster in plasma has been reported in patients with stroke as a potential biomarker for diagnostic and prognostic use. However, the essential role and therapeutic potential of the miR-15a/16-1 cluster in ischemic stroke are poorly understood. This study is aimed at investigating the regulatory role of the miR-15a/16-1 cluster in ischemic brain injury and insight mechanisms. Methods— Adult male miR-15a/16-1 knockout and wild-type mice, or adult male C57 BL/6J mice injected via tail vein with the miR-15a/16-1–specific inhibitor (antagomir, 30 pmol/g), were subjected to 1 hour of middle cerebral artery occlusion and 72 hours of reperfusion. The neurological scores, brain infarct volume, brain water content, and neurobehavioral tests were then evaluated and analyzed. To explore underlying signaling pathways associated with alteration of miR-15a/16-1 activity, major proinflammatory cytokines were measured by quantitative polymerase chain reaction or ELISA and antiapoptotic proteins were examined by Western blotting. Results— Genetic deletion of the miR-15a/16-1 cluster or intravenous delivery of miR-15a/16-1 antagomir significantly reduced cerebral infarct size, decreased brain water content, and improved neurological outcomes in stroke mice. Inhibition of miR-15a/16-1 significantly decreased the expression of the proinflammatory cytokines interleukin-6, monocyte chemoattractant protein-1, vascular cell adhesion molecule 1, tumor necrosis factor alpha, and increased Bcl-2 and Bcl-w levels in the ischemic brain regions. Conclusions— Our data indicate that pharmacological inhibition of the miR-15a/16-1 cluster reduces ischemic brain injury via both upregulation of antiapoptotic proteins and suppression of proinflammatory molecules. These results suggest that the miR-15a/16-1 cluster is a novel therapeutic target for ischemic stroke. |
| Databáze: | OpenAIRE |
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