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Updated: May 23, 2025

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上调的CEMIP通过AP-1介导的染色质可访问性的变化促进椎间盘退化

Shibin Shu¹, Xin Zhang¹, Zhenhua Feng¹

¹Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.

Clinical and translational medicine

|May 22, 2025

概括

椎间盘退化 (IDD) 与表观遗传变化有关. 该研究确定细胞迁移诱导蛋白 (CEMIP) 作为IDD的关键生物标志物和治疗点,由AP-1转录因子调节.

科学领域:

生物医学研究的研究.
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
骨生物学骨生物学

背景情况:

椎间盘退化 (IDD) 是腰部疼痛的主要原因,其特征是细胞外基质 (ECM) 退化和细胞功能障碍.
在IDD期间,表观遗传修饰在细胞核中 (NPCs) 调节基因表达方面发挥着至关重要的作用.

研究的目的:

使用ATAC-seq. 调查退化的NPCs的表观遗传景观.
确定关键的分子参与者和参与IDD病变的调控机制.

主要方法:

用高通量测序 (ATAC-seq) 检测转化酶可访问的染色质,以分析退化NPC中的染色质可访问性.
ATAC-seq和转录概况数据的综合分析.
血CEMIP水平与临床IDD严重程度的相关性分析.
评估CEMIP在IDD小鼠模型中的作用.

主要成果:

激活蛋白-1 (AP-1) 转录因子被确定为IDD中染色质可访问性变化的关键驱动因素.
细胞迁移诱导蛋白 (CEMIP) 被确定为一个关键的生物标志物和IDD的贡献者,显示出显著的上调.
发现AP-1家族,特别是c-Fos,可以调节CEMIP上调.
较高的CEMIP血水平与IDD严重程度相关,而CEMIP淘汰赛小鼠显示IDD表型有所改善.

结论:

通过调节氨酸降解和促进纤维变化,CEMIP扰乱了ECM平衡.
AP-1家族是IDD的关键调节者.
对于新的IDD干预措施来说,CEMIP是一个有前途的治疗目标,有可能减轻背痛的全球负担.

关键词:

在CEMIP中,CEMIP是CEMIP.染色质可访问性染色质可访问性氨酸是什么? 氨酸是什么?椎间盘退化椎间盘退化它的核是脉冲的脉冲.

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