miR-188-5p silencing improves cerebral ischemia/reperfusion injury by targeting Lin28a
Dan Hou1, Chaoying Pei1, Dan Yu2
1Department of Neurology, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, Hainan, 570208, China.
Abstract:
This report aimed to explore whether miR-188-5p regulated the pathological regulatory network of cerebral ischemia/reperfusion (I/R) injury. We simulated the cerebral I/R injury model with MACO/R and OGD/R treatments. Neuronal viability and apoptosis were assessed. The contents of miR-188-5p and Lin 28a were evaluated. The abundances of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were measured. The interaction of miR-188-5p and Lin28a was confirmed. Lin28a silencing was supplemented to determine the delicate regulation of miR-188-5p. We revealed that miR-188-5p was upregulated and Lin28a was downregulated in I/R rats and OGD/R-induced cells. miR-188-5p silencing remarkably reduced the cerebral infarction volume, neurobehavioral score, brain edema, and Evans blue leakage. miR-188-5p silencing enhanced neuronal viability and alleviated apoptosis. The abundance of Bax and cleaved caspase-3 was reduced by miR-188-5p silencing, while Bcl-2 was augmented. miR-188-5p silencing impeded the contents of TNF-α, IL-1β, and IL-6. miR-188-5p interacted with Lin28a and negatively regulated its expression. Interestingly, extra Lin28a silencing reversed apoptosis and the content of inflammatory cytokines. Our studies confirmed that miR-188-5p silencing alleviated neuronal apoptosis and inflammation by mediating the expression of Lin28a. The crosstalk of miR-188-5p and Lin28a offered a different direction for ischemic stroke therapy.
Insights
MicroRNA-188-5p silencing protects against cerebral ischemia/reperfusion (I/R) injury by reducing neuronal apoptosis and inflammation. This occurs through its regulation of Lin28a, offering a new therapeutic target for ischemic stroke.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Cerebral ischemia/reperfusion (I/R) injury involves complex pathological regulatory networks.
- MicroRNAs (miRNAs) play crucial roles in regulating cellular processes, including apoptosis and inflammation.
Purpose of the Study:
- To investigate the role of miR-188-5p in the pathological regulatory network of cerebral I/R injury.
- To elucidate the regulatory relationship between miR-188-5p and Lin28a in this context.
Main Methods:
- Cerebral I/R injury models were established using MACO/R and OGD/R treatments.
- Neuronal viability, apoptosis, protein and cytokine levels, and miRNA/mRNA expression were assessed.
- Interaction between miR-188-5p and Lin28a was confirmed, with Lin28a silencing used to further explore regulatory mechanisms.
Main Results:
- miR-188-5p was upregulated, while Lin28a was downregulated in I/R models.
- Silencing miR-188-5p reduced infarct volume, improved neurobehavioral scores, and decreased brain edema.
- miR-188-5p silencing enhanced neuronal viability, reduced apoptosis, and modulated apoptosis-related proteins (Bax, Bcl-2, cleaved caspase-3) and inflammatory cytokines (TNF-α, IL-1β, IL-6).
- miR-188-5p negatively regulated Lin28a expression, and additional Lin28a silencing reversed the protective effects.
Conclusions:
- miR-188-5p silencing alleviates neuronal apoptosis and inflammation in cerebral I/R injury by mediating Lin28a expression.
- The interaction between miR-188-5p and Lin28a presents a novel therapeutic strategy for ischemic stroke.
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