Tang Tao, Chen Linyi, Zhang Ming, Wang Chuang, Du Xiaolong, Ye Shenglin, Li Xiaoqiang, Chen Hong, Hu Nan
Department of Vascular Surgery, The Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical School, #321 Zhongshan Road, Nanjing, Jiangsu, 210008, China.
Department of Ophthalmology, The Fourth Affiliated Hospital of Nanjing Medical University, #298 Nan Pu Road, Nanjing, Jiangsu, 210008, China.
Diabetol Metab Syndr. 2024 Feb 7;16(1):37. doi: 10.1186/s13098-023-01210-x.
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.
已阐明源自骨髓间充质干细胞（BMSC）的外泌体（Exo）可促进糖尿病（DM）小鼠模型的皮肤伤口愈合。但其潜在机制尚不清楚。
采用下一代测序（NGS）检测Exo处理后circRNA表达水平的变化。使用荧光素酶测定法确定RNA之间的相互作用。采用免疫荧光染色检测在高糖（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Exo的治疗效果。
我们发现Exo处理显著促进了皮肤伤口愈合。NGS表明circ-Snhg11参与了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的下游靶点。miR-144-3p的过表达或SLC7A11的敲低改变了circ-Snhg11对暴露于HG条件下的EPC的保护作用。circ-Snhg11的上调通过增强血管生成以及减少GPX4介导的铁死亡，增加了Exo处理在DM小鼠伤口愈合过程中的治疗效果。
BMSC-Exos中的circ-Snhg11通过miR-144-3p海绵作用增强了SLC7A11/GPX4介导的抗铁死亡信号，从而促进糖尿病伤口愈合并改善血管生成。
