皮肤上的NAD+缺乏会诱导IL-36介导的皮肤炎症和阿坎托सिस
Taiki Seki1, Jun-Dal Kim2, Yasuhito Yahara1
1Department of Molecular and Medical Pharmacology, University of Toyama, Toyama, Japan.
JCI insight
|February 10, 2026
概括
尼古丁胺胺氨基二核酸 (NAD+) 缺乏会损害皮肤平衡,导致炎症和DNA损伤. 使用尼古丁胺胺单核酸 (NMN) 恢复NAD+水平可以减少皮肤炎症,提供治疗潜力.
科学领域:
- 皮肤病学 皮肤病学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 尼古丁胺胺氨基二核酸 (NAD+) 对于细胞功能至关重要,包括新陈代谢,DNA修复和应激反应.
- NAD+的合成依赖于氨酸和氨酸;缺陷会导致皮质炎,特点是皮肤炎,腹和痴呆.
- 佩拉格拉引起的皮肤炎通常呈现为光皮肤病,影响暴露在阳光下的皮肤区域.
研究的目的:
- 为了研究NAD+缺乏对皮肤平衡的影响.
- 探索Nampt介导的NAD+代谢在表皮稳定中的作用.
- 确定将NAD+枯竭与皮肤炎症联系起来的分子机制.
主要方法:
- 利用表皮特异性的Nampt条件淘汰 (cKO) 小鼠诱导NAD+缺乏.
- 在小鼠皮肤中评估了NAD+水平,聚ADP-ribose) 聚合酶 (PARP) 活性和DNA损伤.
- 进行RNA测序和免疫组织化学分析以评估基因和蛋白质表达,包括IL-36和TSLP等细胞因子和原17A1.1.
- 研究了通过皮肤补充尼古丁胺胺 mononucleotide (NMN) 的治疗效果.
主要成果:
- 纳普特cKO小鼠表现出显著的NAD+耗尽,减少PARP活性,并增加DNA损伤.
- 这些小鼠出现了自发的皮肤炎症和表皮层增生症.
- 观察到高联素-36 (IL-36) 细胞因子表达,这表明基因组应激和角质细胞驱动的炎症之间存在联系.
- 发现了降低的原17A1和提升的胸膜层淋巴质素 (TSLP) 水平.
- 通过皮肤NMN补充剂成功降低了IL-36水平,并缓解了皮肤炎症.
结论:
- 纳普特介导的NAD+代谢对于维持表皮稳定性至关重要.
- 缺少NAD+可以触发皮细胞衍生IL-36的产生,导致皮肤炎症.
- 准NAD+代谢和IL-36通路可能为炎症性皮肤疾病提供新的治疗策略.
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