Department of Neurosurgery, Liaocheng People's Hospital, No. 67 Dongchang West Road, Liaocheng, 252000, China.
Department of Laboratory, Liaocheng Maternal and Child Health Care Hospital, No.56, Changjiang Road, Liaocheng, 252000, Shandong, China.
Appl Biochem Biotechnol. 2024 Sep;196(9):5920-5935. doi: 10.1007/s12010-023-04836-9. Epub 2024 Jan 2.
Spinal cord injury (SCI) is a highly debilitating disorder of the central nervous system that can severely impact an affected patient's quality of life. This study aimed to examine how adipose-derived mesenchymal stem cell exosomes (ADSC-exos) can be used to treat spinal cord injury. We analysed differentially expressed mRNAs in SCI using bioinformatics data, gene expression profiles in inflammatory cell models, RT-qPCR and WB. Apoptosis was detected with flow cytometry. Starbase provides the control mechanism for FDFT1. Target interactions were detected with dual-luciferase reporter and RIP assays. Exosomes were isolated from adipose tissue-derived mesenchymal stem cells and subsequently characterized with western blot analysis, transmission electron microscopy and nanoparticle tracking analysis. By analysing the GSE102964 database, we found that FDFT1 was significantly downregulated as SCI progressed. Overexpression of FDFT1 can significantly reverse the inflammatory response and apoptosis of BV2 cells induced by hemin. Mechanically, ADSC-exos can affect the expression of FDFT1 through the ceRNA mechanism mediated by LRRC75A-AS1 and in an RBP-dependent manner mediated by IGF2BP2. The overexpression of LRRC75A-AS1 significantly enhances BV2 apoptosis and can be reversed by FDFT1 knockdown. ADSC-exos LRRC75A-AS1 inhibits inflammation and reduces SCI by increasing the expression and stability of FDFT1 mRNA in a ceRNA and RBP-dependent manner.
脊髓损伤 (SCI) 是一种高度使人虚弱的中枢神经系统疾病,会严重影响受影响患者的生活质量。本研究旨在探讨脂肪来源间充质干细胞外泌体 (ADSC-exos) 如何用于治疗脊髓损伤。我们使用生物信息学数据、炎症细胞模型中的基因表达谱、RT-qPCR 和 WB 分析了 SCI 中的差异表达 mRNA。通过流式细胞术检测细胞凋亡。Starbase 为 FDFT1 提供了对照机制。通过双荧光素酶报告和 RIP 测定检测靶标相互作用。从脂肪组织来源的间充质干细胞中分离外泌体,并通过 Western blot 分析、透射电子显微镜和纳米颗粒跟踪分析对其进行鉴定。通过分析 GSE102964 数据库,我们发现随着 SCI 的进展,FDFT1 表达显著下调。FDFT1 的过表达可显著逆转 hemin 诱导的 BV2 细胞炎症反应和细胞凋亡。在机制上,ADSC-exos 可以通过 LRRC75A-AS1 介导的 ceRNA 机制和 IGF2BP2 介导的 RBP 依赖性方式影响 FDFT1 的表达。LRRC75A-AS1 的过表达显著增强了 BV2 细胞凋亡,而 FDFT1 的敲低可以逆转这一现象。ADSC-exos 通过依赖 ceRNA 和 RBP 的方式增加 FDFT1 mRNA 的表达和稳定性,抑制炎症反应,减少 SCI。