Exosomes (Exos) generated from bone mesenchymal stem cells (BMSCs) are elucidated to enhance cutaneous wound healing in mice models of diabetes mellitus (DM). While underlying mechanisms remain unknown. Next-generation sequencing (NGS) was used to examine changes in circRNA expression levels following Exo treatment. Luciferase assays were used to determine the interactions between RNAs. Immunofluorescence staining was used to examine reactive oxygen species (ROS) in endothelial progenitor cells (EPCs) cultured in high glucose (HG) conditions. Therapeutic effects regarding Exos were also examined by immunofluorescence. We found that Exo treatment enhanced cutaneous wound healing significantly. NGS indicated that circ-Snhg11 was involved in Exo-mediated tissue repairing. Downregulation of circ-Snhg11 decreased Exo-mediated therapy responses during wound healing in diabetic mouse. Our luciferase reporter data confirmed that SLC7A11 and miR-144-3p were circ-Snhg11 downstream targets. miR-144-3p overexpression or SLC7A11 knockdown altered the protective effects of circ-Snhg11 upon EPCs exposed to HG conditions. Upregulation of circ-Snhg11 incremented therapy effects of Exo treatment during wound healing in DM mice through enhanced angiogenesis along with a reduction in GPX4-mediated ferroptosis. circ-Snhg11 in BMSC-Exos enhanced SLC7A11/GPX4-mediated anti-ferroptosis signals via miR-144-3p sponging resulting in enhanced diabetic wound healing and improved angiopoiesis.

中文翻译：

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来自 BMSC 的外泌体通过 circ-Snhg11 传递增强糖尿病伤口愈合

研究表明，由骨间充质干细胞 (BMSC) 产生的外泌体 (Exos) 可增强糖尿病 (DM) 小鼠模型的皮肤伤口愈合。虽然潜在的机制仍然未知。新一代测序 (NGS) 用于检查 Exo 处理后 circRNA 表达水平的变化。荧光素酶测定用于确定 RNA 之间的相互作用。免疫荧光染色用于检查高葡萄糖 (HG) 条件下培养的内皮祖细胞 (EPC) 中的活性氧 (ROS)。还通过免疫荧光检查了 Exos 的治疗效果。我们发现 Exo 治疗显着促进皮肤伤口愈合。 NGS 表明 circ-Snhg11 参与 Exo 介导的组织修复。 circ-Snhg11 的下调降低了糖尿病小鼠伤口愈合过程中 Exo 介导的治疗反应。我们的荧光素酶报告基因数据证实 SLC7A11 和 miR-144-3p 是 circ-Snhg11 下游靶标。 miR-144-3p 过表达或 SLC7A11 敲低改变了 circ-Snhg11 对暴露于 HG 条件的 EPC 的保护作用。上调 circ-Snhg11 通过增强血管生成以及减少 GPX4 介导的铁死亡，增强了 DM 小鼠伤口愈合过程中 Exo 治疗的治疗效果。 BMSC-Exos 中的 circ-Snhg11 通过 miR-144-3p 海绵作用增强 SLC7A11/GPX4 介导的抗铁死亡信号，从而增强糖尿病伤口愈合并改善血管生成。