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A Simple Alternative to Stereotactic Injection for Brain Specific Knockdown of miRNA
Published on: December 26, 2015
MicroRNA-29b is a therapeutic target in cerebral ischemia associated with aquaporin 4
Yang Wang1, Jun Huang2, Yuanyuan Ma1
1Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Abstract:
MicroRNA-29b (miR-29b) is involved in regulating ischemia process, but the molecular mechanism is unclear. In this work, we explored the function of miR-29b in cerebral ischemia. The level of miR-29b in white blood cells was evaluated in patients and mice after ischemic stroke. Brain infarct volume and National Institute of Health stroke scale (NIHSS) scores were analyzed to determine the relationship between miR-29b expression and the severity of stroke. The relationship of miR-29b and aquaporin-4 (AQP4) was further studied in mice. We found that miR-29b was significantly downregulated in stroke patients (P<0.05). MiR-29b level negatively associated with NIHSS scores (r=-0.349, P<0.01) and brain infarct volume (r=-0.321, P<0.05). In ischemic mice, miR-29b in the brain and blood were both downregulated (r=0.723, P<0.05). MiR-29b overexpression reduced infarct volume (49.50±6.55 versus 35.48±2.28 mm(3), P<0.05), edema (164±4% versus 108±4%, P<0.05), and blood-brain barrier (BBB) disruption compared with controls (15±9% versus 7±3%, P<0.05). Aquaporin-4 expression greatly decreased after miR-29b overexpression (28±7% versus 11±3%, P<0.05). Dual-luciferase reporter system showed that AQP-4 was the direct target of miR-29b (P<0.05). We concluded that miR-29b could potentially predict stroke outcomes as a novel circulating biomarker, and miR-29b overexpression reduced BBB disruption after ischemic stroke via downregulating AQP-4.
Insights
MicroRNA-29b (miR-29b) levels decrease in stroke patients and mice. Overexpressing miR-29b reduces stroke damage by downregulating aquaporin-4, suggesting miR-29b as a potential biomarker.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Cerebral ischemia involves microRNA-29b (miR-29b), but its precise role and mechanism remain unclear.
- Understanding miR-29b's function is crucial for developing new therapeutic strategies for ischemic stroke.
Purpose of the Study:
- To investigate the function of miR-29b in cerebral ischemia.
- To explore miR-29b as a potential circulating biomarker for stroke outcomes.
- To elucidate the molecular mechanism of miR-29b in regulating ischemic stroke.
Main Methods:
- Assessed miR-29b levels in white blood cells of stroke patients and mice.
- Analyzed brain infarct volume and NIH stroke scale (NIHSS) scores.
- Investigated the relationship between miR-29b and aquaporin-4 (AQP4) in mice using overexpression models and a dual-luciferase reporter system.
Main Results:
- miR-29b was significantly downregulated in stroke patients and ischemic mice.
- Lower miR-29b levels correlated with increased stroke severity (NIHSS scores) and brain infarct volume.
- Overexpression of miR-29b reduced infarct volume, edema, and blood-brain barrier (BBB) disruption.
- miR-29b directly targets and downregulates AQP4 expression.
Conclusions:
- miR-29b may serve as a novel circulating biomarker for predicting stroke outcomes.
- Overexpression of miR-29b mitigates ischemic stroke damage, particularly BBB disruption, by downregulating AQP4.
