Jiang Zhensong, Zhang Weimin, Zhang Jianru
Department of Spine Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
Department of Health Examination, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, Shandong, China.
Heliyon. 2024 Sep 10;10(18):e37704. doi: 10.1016/j.heliyon.2024.e37704. eCollection 2024 Sep 30.
Ferroptosis is an important way of neuronal cell death in acute phase and participates in the inflammatory cascade after spinal cord injury (SCI). It is reported that microRNA (miRNA) and long non-coding RNA (lncRNA) are key mediators in the regulation of ferroptosis. This study will explore the inhibitory effect of LncRNA OIP5-AS1 on ferroptosis and mitochondrial dysfunction-mediated apoptosis in SCI.
The ferric ammonium citrate (FAC)-induced cell model and the SCI rat model were established. The expression of LncRNA OIP5-AS1, miR-128-3p and Nrf2 were transfected to evaluated the effect on the viability and apoptosis of FAC-induced cell. The interaction between LncRNA OIP5-AS1 and miR-128-3p or miR-128-3p and Nrf2 were analyzed. In addition, expressions of markers related to ferroptosis and mitochondrial dysfunction were analyzed in vitro and in vivo. Histopathologic slide staining was used to analyze spinal cord injury in vivo.
LncRNA OIP5-AS1 expression was abnormally down-regulated in FAC-induced SCI cell model and SCI rats. The LncRNA OIP5-AS1 deficiency induced decreased Nrf2 level by less sponging miR-128-3p, thus, aggravating spinal cord injury and inducing more apoptosis, ferroptosis and mitochondrial dysfunction in neural stem cells with SCI. However, overexpression of LncRNA OIP5-AS1 inhibited apoptosis, ferroptosis and mitochondrial dysfunction, thus effectively ameliorating spinal cord injury.
This finding demonstrates that LncRNA OIP5-AS1 overexpression could enhance the recovery of spinal cord injury by regulating the miR-128-3p/Nrf2 axis.
铁死亡是急性期神经元细胞死亡的重要方式，并参与脊髓损伤（SCI）后的炎症级联反应。据报道，微小RNA（miRNA）和长链非编码RNA（lncRNA）是铁死亡调控中的关键介质。本研究将探讨长链非编码RNA OIP5-AS1对脊髓损伤中铁死亡及线粒体功能障碍介导的细胞凋亡的抑制作用。
建立柠檬酸铁铵（FAC）诱导的细胞模型和脊髓损伤大鼠模型。转染长链非编码RNA OIP5-AS1、miR-128-3p和Nrf2的表达，以评估对FAC诱导细胞的活力和凋亡的影响。分析长链非编码RNA OIP5-AS1与miR-128-3p或miR-128-3p与Nrf2之间的相互作用。此外，在体外和体内分析与铁死亡和线粒体功能障碍相关的标志物的表达。采用组织病理学玻片染色分析体内脊髓损伤情况。
在FAC诱导的脊髓损伤细胞模型和脊髓损伤大鼠中，长链非编码RNA OIP5-AS1表达异常下调。长链非编码RNA OIP5-AS1缺乏通过较少地吸附miR-128-3p导致Nrf2水平降低，从而加重脊髓损伤，并在脊髓损伤的神经干细胞中诱导更多的细胞凋亡、铁死亡和线粒体功能障碍。然而，长链非编码RNA OIP5-AS1的过表达抑制了细胞凋亡、铁死亡和线粒体功能障碍，从而有效改善了脊髓损伤。
这一发现表明，长链非编码RNA OIP5-AS1的过表达可通过调节miR-128-3p/Nrf2轴增强脊髓损伤的恢复。
