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.
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All data generated during this study are included in this article. Further enquiries can be directed to the corresponding author.
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Funding
This study were supported by Hainan Province Clinical Medical Center, Hainan Provincial Natural Science Foundation of China (2019RC386), and Science and Technology special fund of Hainan Province (ZDYF2023SHFZ105).
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D Y and GS Y conceived the study, provided research ideas and methods. D H and CY P conducted the experiments and analyzed the data. D H and CY P wrote the draft Manuscript, D Y and GS Y reviewed and edited the manuscript. All authors read and approved the final version.
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Animal studies were approved by the Animal Ethical and Welfare Committee of 351 Central South University Xiangya School of Medicine Affiliated Haikou Hospital (2022 − 203). The studies followed the principles of the Declaration of Helsinki.
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Hou, D., Pei, C., Yu, D. et al. miR-188-5p silencing improves cerebral ischemia/reperfusion injury by targeting Lin28a. Metab Brain Dis 38, 2327–2338 (2023). https://doi.org/10.1007/s11011-023-01273-9
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DOI: https://doi.org/10.1007/s11011-023-01273-9