miR-181b regulates ER stress induced neuron death through targeting Heat Shock Protein A5 following intracerebral haemorrhage.

Endoplasmic reticulum (ER) stress acts as a protein folding and contributes to neuronal damage and neurological deterioration following intracerebral hemorrhage (ICH). Heat Shock Protein A5 (HSPA5) serves as an essential regulator of the endoplasmic reticulum (ER) stress response. However, the specific mechanism has not been will identified. Primary cortical neurons from C57BL/6 mice were subjected to erythrocyte lysates. Cell viability, microRNA and HSPA5 levels, and ER stress was detected. The interaction between microRNA and the target HSPA5 was identified by dual luciferase reporter gene assay. In addition, inflammatory cytokines, brain edema, and neurological functions in ICH mice were also assessed. Erythrocyte lysates induced ER stress and neuron damage, downregulated miR-181b and upregulated HSPA5 levels. MiR-181b suppressed HSPA5 expression by directly binding its 3'-untranslated region. Correspondingly, our data demonstrated that overexpression of miR-181b attenuated erythrocyte lysates induced neuronal necrosis and apoptosis. In vivo, downregulated miR-181b increased the HSPA5 level, along with significant elevations of pro-inflammatory cytokines, brain edema, and neurological injury following ICH. HSPA5 pathway plays an important role in ER stress induced brain damage following ICH. In addition, miR-181b has neuroprotective effects that alleviates neurological injury and represents a promising therapeutic strategy in ICH.

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