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首页> 外文期刊>Cell Division >A positive feedback loop between EZH2 and NOX4 regulates nucleus pulposus cell senescence in age-related intervertebral disc degeneration
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A positive feedback loop between EZH2 and NOX4 regulates nucleus pulposus cell senescence in age-related intervertebral disc degeneration

机译：EZH2和NOx4之间的阳性反馈环度调节年龄相关的椎间盘变性中的核拷贝细胞衰老

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摘要

The senescence of nucleus pulposus (NP) cells plays a vital role in the pathogenesis of intervertebral disc (IVD) degeneration (IDD). NADPH oxidase 4 (NOX4)-associated oxidative stress has been shown to induce premature NP cell senescence. Enhancer of zeste homolog 2 (EZH2) is a crucial gene regulating cell senescence. The aim of this study was to investigate the roles of EZH2 in NOX4-induced NP cell senescence and a feedback loop between EZH2 and NOX4. The down-regulation of EZH2 and the up-regulation of NOX4 and p16 were observed in the degenerative discs of aging rats. EZH2 regulated NP cell senescence via the H3K27me3-p16 pathway. Also, EZH2 regulated the expression of NOX4 in NP cells through the histone H3 lysine 27 trimethylation (H3K27me3) in the promoter of NOX4 gene. Furthermore, NOX4 down-regulated EZH2 expression in NP cells via the canonical Wnt/β-catenin pathway. A positive feedback loop between EZH2 and NOX4 is involved in regulating NP cell senescence, which provides a novel insight into the mechanism of IDD and a potential therapeutic target for IDD.
机译：细胞核拷贝（NP）细胞的衰老在椎间盘（IVD）变性（IDD）的发病机制中起着至关重要的作用。已显示NADPH氧化酶4（NOX4）氧化氧化应激诱导早熟的NP细胞衰老。 Zeste同源物2（EZH2）的增强剂是调节细胞衰老的重要基因。本研究的目的是探讨EZH2在NOX4诱导的NP细胞衰老中的作用和EZH2和NOX4之间的反馈环。在老化大鼠的退行性椎间盘中观察到EZH2和NOx4和P16的上调的下调。 EZH2通过H3K27ME3-P16途径调节NP细胞衰老。此外，EZH2通过NOx4基因的启动子中的组蛋白H3赖氨酸27三甲基化（H3K27ME3）调节NOx4在NP细胞中的表达。此外，通过规范Wnt /β-catenin途径，NOx4下调在NP细胞中的表达。 EZH2和NOX4之间的阳性反馈环涉及调节NP细胞衰老，这提供了对IDD机制和IDD的潜在治疗目标的新颖洞察力。

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