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环状 RNA Hecw1 通过 miR-3551-3p/LRRTM1 轴调控脊髓损伤中的炎症失衡。

Circular RNA Hecw1 Regulates the Inflammatory Imbalance in Spinal Cord Injury via miR-3551-3p/LRRTM1 Axis.

机构信息

Department of Orthopaedics, Tianjin Medical University General Hospital, TianjinHepingDistrict, No. 154, Anshan Road, Tianjin, 300052, People's Republic of China.

出版信息

Appl Biochem Biotechnol. 2022 Nov;194(11):5151-5166. doi: 10.1007/s12010-022-03999-1. Epub 2022 Jun 14.

Abstract

Spinal cord injury (SCI) is a neurological disease having devastating effect and results in the development of systemic inflammation. However, the molecular mechanisms of SCI remain not entirely elucidated. This study was directed toward exploring the circ Hecw1 involved in the mechanism of lipopolysaccharide (LPS)-triggered inflammation damage in neuronal cells. The in vitro model of SCI based on PC12 cells were established with lipopolysaccharide. The cell proliferation was determined by the use of cell counting kit-8 (CCK8). The expressions of circHecw1, miR-3551-3p, and inflammatory factors were measured by quantitative real-time PCR and ELISA assay. Flow cytometry was used to assess apoptosis. Western blot analysis was performed for the purpose of determining LRRTM1 and NF-kB signaling. The expression of circ Hecw1, TNF-α, IL-6, and IL-1β in LPS-triggered PC12 cells and the expression of miR-3551-3p and IL-10 were significantly decreased. Knockdown of circHecw1 promoted proliferation and inhibited apoptosis and reduction in the inflammatory cytokine expression. Our study revealed that circHecw1 regulates SCI neuronal cell inflammation imbalance by regulating the miR-3551-3p/LRRTM1 signaling.

摘要

脊髓损伤 (SCI) 是一种具有破坏性影响的神经系统疾病,会导致全身炎症的发展。然而,SCI 的分子机制仍不完全清楚。本研究旨在探讨 circHecw1 在脂多糖 (LPS) 触发神经元细胞炎症损伤机制中的作用。利用脂多糖建立了基于 PC12 细胞的 SCI 体外模型。通过细胞计数试剂盒-8 (CCK8) 测定细胞增殖。采用定量实时 PCR 和 ELISA 测定 circHecw1、miR-3551-3p 和炎症因子的表达。采用流式细胞术评估细胞凋亡。采用 Western blot 分析测定 LRRTM1 和 NF-κB 信号通路。LPS 触发的 PC12 细胞中 circHecw1、TNF-α、IL-6 和 IL-1β 的表达以及 miR-3551-3p 和 IL-10 的表达均显著降低。circHecw1 的敲低促进了增殖,抑制了凋亡,并减少了炎症细胞因子的表达。我们的研究表明,circHecw1 通过调节 miR-3551-3p/LRRTM1 信号通路来调节 SCI 神经元细胞炎症失衡。

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