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长链非编码 RNA HCG18 通过 miR-495-3p/FSTL1 轴促进椎间盘退变中的炎症和细胞凋亡。

LncRNA HCG18 promotes inflammation and apoptosis in intervertebral disc degeneration via the miR-495-3p/FSTL1 axis.

机构信息

The Affiliated Changsha Central Hospital, Department of Spine Surgery, Hengyang Medical School, University of South China, Changsha, No. 161, The Shaoshan South Road, Changsha, 410007, Hunan, People's Republic of China.

出版信息

Mol Cell Biochem. 2024 Jan;479(1):171-181. doi: 10.1007/s11010-023-04716-0. Epub 2023 May 3.

DOI:10.1007/s11010-023-04716-0
PMID:37138144
Abstract

Intervertebral disc degeneration (IDD) causes pain in the back and neck. This study investigated the role of long non-coding RNA HLA complex group 18 (HCG18) in a cell model of IDD. An IDD model was established by stimulating nucleus pulposus (NP) cells with interleukin (IL)-1β. MTT assay was performed to evaluate NP cell viability. The apoptosis was detected by flow cytometry. The expressions of HCG18, microRNA (miR)-495-3p, and follistatin-like protein-1 (FSTL1) were measured by RT-qPCR. The interactions of miR-495-3p with HCG18 and FSTL1 were analyzed by luciferase reporter assay. IL-1β stimulation upregulated HCG18 and FSTL1, but downregulated miR-495-3p in NP cells. Silencing of HCG18 or FSTL1, as well as miR-495-3p overexpression in NP cells alleviated IL-1β-induced apoptosis and inflammation of NP cells. Both HCG18 and FSTL1 had binding sites for miR-495-3p. Overexpression of FSTL1 abolished the effects of HCG18 silencing on IL-1β-induced apoptosis and inflammation. The HCG18/miR-495-3p/FSTL1 axis is essential for IDD development. Therapeutic strategies targeting this axis may be used for IDD treatment.

摘要

椎间盘退行性变(IDD)会引起背部和颈部疼痛。本研究探讨了长非编码 RNA HLA 复合体 18 (HCG18)在 IDD 细胞模型中的作用。通过用白细胞介素(IL)-1β刺激髓核(NP)细胞来建立 IDD 模型。通过 MTT 测定法评估 NP 细胞活力。通过流式细胞术检测细胞凋亡。通过 RT-qPCR 测量 HCG18、微小 RNA(miR)-495-3p 和卵泡抑素样蛋白-1(FSTL1)的表达。通过荧光素酶报告测定分析 miR-495-3p 与 HCG18 和 FSTL1 的相互作用。IL-1β 刺激可上调 NP 细胞中的 HCG18 和 FSTL1,但下调 miR-495-3p。NP 细胞中 HCG18 或 FSTL1 的沉默以及 miR-495-3p 的过表达可减轻 IL-1β 诱导的 NP 细胞凋亡和炎症。HCG18 和 FSTL1 均具有 miR-495-3p 的结合位点。FSTL1 的过表达消除了 HCG18 沉默对 IL-1β 诱导的凋亡和炎症的影响。HCG18/miR-495-3p/FSTL1 轴对于 IDD 的发展至关重要。针对该轴的治疗策略可用于治疗 IDD。

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本文引用的文献

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Targeting clock-controlled gene Nrf2 ameliorates inflammation-induced intervertebral disc degeneration.靶向调控生物钟基因 Nrf2 可改善炎症诱导的椎间盘退变。
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富马酸二甲酯可保护髓核细胞免受炎症和氧化应激的影响,并延缓椎间盘退变。
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