Chang Liu, Libangxi Liu, Minghui Yang, Bin Li, Jiarong Yi, Xuezheng Ai, Yang Zhang, Bo Huang, Changqing Li, Chencheng Feng, Yue Zhou
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引用次数: 16
摘要
背景:髓核(NP)细胞的衰老在椎间盘退变(IDD)的发病机制中起着至关重要的作用。NADPH氧化酶4 (NOX4)相关的氧化应激已被证明可诱导NP细胞过早衰老。zeste同源物2增强子(Enhancer of zeste homolog 2, EZH2)是调控细胞衰老的重要基因。本研究旨在探讨EZH2在NOX4诱导的NP细胞衰老中的作用以及EZH2和NOX4之间的反馈回路。结果:衰老大鼠退行性椎间盘中EZH2表达下调，NOX4、p16表达上调。EZH2通过H3K27me3-p16通路调控NP细胞衰老。EZH2通过NOX4基因启动子组蛋白H3赖氨酸27三甲基化(H3K27me3)调节NOX4在NP细胞中的表达。此外，NOX4通过典型的Wnt/β-catenin途径下调NP细胞中EZH2的表达。结论:EZH2和NOX4之间的正反馈回路参与了NP细胞衰老的调控，这为IDD的机制提供了新的认识，并为IDD的潜在治疗靶点提供了新的思路。
A positive feedback loop between EZH2 and NOX4 regulates nucleus pulposus cell senescence in age-related intervertebral disc degeneration.
Background: 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.
Results: 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.
Conclusions: 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.
期刊介绍：
Cell Division is an open access, peer-reviewed journal that encompasses all the molecular aspects of cell cycle control and cancer, cell growth, proliferation, survival, differentiation, signalling, gene transcription, protein synthesis, genome integrity, chromosome stability, centrosome duplication, DNA damage and DNA repair.
Cell Division provides an online forum for the cell-cycle community that aims to publish articles on all exciting aspects of cell-cycle research and to bridge the gap between models of cell cycle regulation, development, and cancer biology. This forum is driven by specialized and timely research articles, reviews and commentaries focused on this fast moving field, providing an invaluable tool for cell-cycle biologists.
Cell Division publishes articles in areas which includes, but not limited to:
DNA replication, cell fate decisions, cell cycle & development
Cell proliferation, mitosis, spindle assembly checkpoint, ubiquitin mediated degradation
DNA damage & repair
Apoptosis & cell death
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