TET2通过激活RIPK3-MLKL-necroptosis信号来促进UVB诱导的细胞死亡
Daijing Long1, Yangfan Xu1, Xuemei Li1
1Department of Dermatology, Central South University Third Xiangya Hospital, 138 Tongzipo Road, Yuelu District, Changsha, Hunan Province, 410013, PR China.
十一转位2 (TET2) 蛋白质通过激活RIPK3-MLKL通路,促进UVB辐射对皮肤的损伤. 降低TET2水平可以保护皮肤细胞免受光损伤和细胞死亡.
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:
- 紫外线B (UVB) 辐射是造成皮肤光损伤的主要原因.
- 导致UVB引起的光损伤的精确分子机制尚未完全理解.
- 之前的研究表明,十-十一转位2 (TET2) 在暴露于UVB的角质细胞中被上调.
研究的目的:
- 研究TET2在UVB引起的皮肤光损伤中的作用.
- 阐明TET2调解光损伤的分子途径.
主要方法:
- 在人类和小鼠皮肤样本中分析TET2表达.
- 在体外研究中,使用具有操纵TET2水平 (缺乏和过度表达) 的角质细胞.
- 对RIPK3-MLKL和caspase-8信号通路的研究.
主要成果:
- 来自患者和动物模型的光损伤皮肤中的TET2被上调.
- 由于TET2缺乏,可以减少UVB诱导的角质细胞死亡和光损伤.
- 过度表达TET2恶化了UVB的影响.
- TET2通过DNA脱甲基化和PLK3结合激活RIPK3-MLKL通路,其中二次涉及酶-8.
结论:
- TET2在介导UVB诱导的角质细胞死亡和光损伤方面发挥着重要作用.
- TET2通过激活RIPK3-MLKL信号通路来协调宿主对UVB暴露的反应.
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