Intracerebral hemorrhage (ICH) has a high rate of death and disability. LncRNA-TUG1 is essential for the pathological changes secondary to ICH. The purpose of this work was to investigate the possible Show more
Intracerebral hemorrhage (ICH) has a high rate of death and disability. LncRNA-TUG1 is essential for the pathological changes secondary to ICH. The purpose of this work was to investigate the possible mechanism by which TUG1 inhibits neural repair subsequent to ICH through adjusting miR-381-3p/brain-derived neurotrophic factor (BDNF). After the ICH model was created, miR-381-3p agomir and pcDNA-TUG1 were injected. The neural function of rats was estimated using the modified neurological severity score. To quantify the expression of genes and proteins, western blotting, immunohistochemistry, and qRT-PCR were used. To confirm the interaction between TUG1 and miR-381-3p and between miR-381-3p and BDNF mRNA, a luciferase reporter assay was employed. In rats treated with miR-381-3p agomir, a trend of improvement in neurological dysfunction was observed, while the pcDNA-TUG1-treated ones showed deterioration. Furthermore, miR-381-3p agomir increased, while pcDNA-TUG1 reduced the expression level of BDNF in ICH rats. TUG1 and BDNF mRNA were validated to attach directly to miR-381-3p. Overexpressing TUG1 inhibited the level of BDNF by sponging miR-381-3p and antagonized its protective effect on neural repair in ICH rats. Our study suggests that TUG1 can sponge miR-381-3p to downregulate BDNF expression and inhibit neural repair following ICH, demonstrating a potential signaling pathway that is conducive to a better understanding of the pathological mechanisms of ICH. Show less
Peripheral nerve injury is a salient clinical problem but lacks successful treatment schemes. Here we show the protective mechanism of hypoxia-induced Schwann cells-derived extracellular vesicles (H-E Show more
Peripheral nerve injury is a salient clinical problem but lacks successful treatment schemes. Here we show the protective mechanism of hypoxia-induced Schwann cells-derived extracellular vesicles (H-EVs) carrying lncRNA TNXA-PS1 in peripheral nerve injury. EVs isolated from RSC96 cells undergo hypoxia (H) induction. Sciatic nerve injury is induced in rats, and the animals are evaluated by Sciatic Nerve Function Index, gastrocnemius muscle mass ratio, hematoxylin & eosin stain, and sensory recovery tests. LncRNA TNXA-PS1, miR-338-3p, and EGFL7 expression is tested by RT-qPCR and Western blot. Proliferation, migration, and angiogenesis of H-EVs- treated endothelial cells are assessed by CCK-8, EdU staining, transwell, and tubular formation assays. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NF200, P0, CD31, and vascular endothelial growth factor (VEGF) are detected. Dual luciferase assay analyzes the binding of lncRNA TNXA-PS1, miR-338-3p, and EGFL7. Results reveal that H-EVs alleviate gastrocnemius muscle atrophy, facilitate motor function recovery, and elevate NGF, BDNF, NF200, P0, CD31, and VEGF in tissues. H-EVs promote endothelial cell proliferation, migration, and tubular formation. Mechanistically, H-EVs carry lncRNA TNXA-PS1 into endothelial cells, thus upregulating EGFL7 expression by sponging miR-338-3p. Collectively, H-EVs carrying lncRNA TNXA-PS1 promote angiogenesis and nerve function recovery post sciatic nerve injury via miR-338-3p/EGFL7 axis. Show less