热应力调节WDR5-介导的H3K4me3修饰通过激活CX3CL1/CX3CR1轴来诱导黑色素形成
Yushan Zhang1, Ling Jiang1, Yibo Hu2
1Department of Dermatology, The Third Xiangya Hospital, Central South University, Changsha, 410013, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|November 21, 2025
概括
热应激通过MYC-WDR5-H3K4me3通路增加CX3CL1 (fractalkine),激活CX3CL1/CX3CR1-JNK信号级联,从而导致皮肤多颜色. 这揭示了颜色系疾病的新治疗点.
科学领域:
- 皮肤病学 皮肤病学
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 皮肤的热敏性使其对热应激产生反应,破坏平衡,并激活色素通路.
- 热应激在临床上与多颜色化有关,但分子机制,特别是表观遗传与免疫交叉,仍然不清楚.
- 黑色素瘤的转录组分析显示了CX3CL1和黑色素形成之间的相关性.
研究的目的:
- 为了阐明热引起的黑色素发生的分子机制.
- 为了研究表观遗传-免疫交叉在热引起的皮肤颜色的作用.
- 为了确定色素皮肤疾病的新型治疗点.
主要方法:
- 瘤样本的转录基因分析.
- 使用培养皮肤组织和黑色素细胞进行体外研究.
- 对MYC-WDR5-H3K4me3轴和CX3CL1/CX3CR1-JNK信号通路的研究.
主要成果:
- 通过依赖CX3CR1的JNK通路激活,CX3CL1显著增强了黑色素的产生.
- 热应激将WDR5招募到CX3CL1促进体,催化H3K4me3修饰并增加CX3CL1转录.
- MYC对于WDR5对CX3CL1促进体的招募至关重要,而WDR5抑制可以逆转热引起的黑色素发生.
结论:
- 热应激通过MYC-WDR5-H3K4me3轴对CX3CL1进行上调,促进黑色素的产生.
- CX3CL1/CX3CR1-JNK信号通路对于热引起的皮肤颜色变化至关重要.
- 这项研究确定了MYC-WDR5-H3K4me3-CX3CL1轴作为颜色系疾病的关键机制和潜在治疗标.
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