LncRNA NORAD缺陷恶化了与年龄相关的黄斑退行症的形成
Jinfeng Zhang1, Jing Jiang1, Hongyu Zhou1
1College of Pharmacy, Binzhou Medical University, Shandong, China.
Aging
|July 30, 2023
概括
由DNA损伤激活的长非编码RNA (NORAD) 通过促进视网膜细胞衰老和亡来加速与年龄相关的黄斑变性 (AMD). 诺拉德缺陷加剧了AMD标志物和线粒体功能障碍.
科学领域:
- 眼科医生 眼科 眼科
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 长非编码RNAs (lncRNAs) 涉及与年龄相关的黄斑变性 (AMD) 病原体.
- 在AMD中,由DNA损伤激活的长非编码RNA (NORAD) 的特定作用仍然未被描述.
研究的目的:
- 在AMD模型中调查NORAD对视网膜色素上皮细胞 (RPE) 衰老和退化的影响.
主要方法:
- 已建立的 *in vitro* (辐射ARPE-19细胞) 和 *in vivo* (用酸盐治疗的小鼠) AMD模型.
- 利用诺拉德的击倒和淘汰战略.
- 评估了细胞周期,细胞亡,衰老,基因表达 (AMD因子,线粒体基因),PGC-1α乙化,线粒体活性氧物种 (ROS),以及视网膜结构/功能.
主要成果:
- 诺拉德突击加剧了辐射诱导的RPE细胞衰老,细胞亡,细胞循环停止 (G2/M) 和增加p-P53/P21表达.
- 抑制NORAD增加了AMD相关因子 (C3,ICAM-1,APP,APOE,VEGF-A) 和降低了线粒体平衡 (TFAM,POLG) 和呼吸链基因表达 (ND1,ND5).
- 在小鼠中,NORAD缺乏增加了PGC-1α乙化,线粒体ROS,并加速了视网膜退化,这表明NORAD有保护作用.
结论:
- 诺拉德缺乏加速RPE细胞衰老,细胞亡和AMD进展.
- 诺拉德通过PGC-1α乙化,线粒体ROS调节和p-P53-P21信号通路影响AMD的发病.
- 诺拉德可以通过与PGC-1α和SIRT1的相互作用来施加其保护作用,调节PGC-1α乙化.
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