基碳化合物受体通过暂时激活TFAP2A调节表皮分化
Jos P H Smits1,2, Jieqiong Qu3, Felicitas Pardow1,3
1Department of Dermatology, Radboud Research Institute for Medical Innovation, Radboudumc, Nijmegen, The Netherlands.
bioRxiv : the preprint server for biology
|June 19, 2023
概括
酸受体 (AHR) 通过激活像TFAP2A.A.这样的转录因子来调节皮肤屏障功能. 这一途径对于状细胞的分化和维持上皮质平衡至关重要.
科学领域:
- 皮肤病学 皮肤病学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 基碳化合物受体 (AHR) 是一个关键的环境传感器,它调节了上皮质恒温.
- 在屏障器官中AHR信号传递的精确分子机制和向基因仍然不完全理解.
研究的目的:
- 阐明在人类皮肤角质细胞中由AHR激活启动的分子信号级联.
- 为了确定关键的转录因子和下游基因参与AHR介导的上皮质屏障功能.
主要方法:
- 人体皮肤角质细胞的多组分析.
- 染色体结合测定用于识别AHR目标.
- 在人类表皮相应物中进行CRISPR/Cas9基因编辑.
主要成果:
- 通过激活AHR,通过与开放色素结合,迅速诱导转录因子,包括TFAP2A.
- TFAP2A调解了二次反应,对像菲拉格林和角质蛋白这样的屏障基因进行上调,以实现终端分化.
- 证实,AHR-TFAP2A轴控制了角质细胞分化和屏障形成.
结论:
- 这项研究揭示了一种新的AHR-TFAP2A信号轴,该轴对于皮肤屏障功能至关重要.
- 这项研究为治疗皮肤屏障疾病提供了新的分子标.
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