牛皮皮肤转录表型:雄激素/雌激素和皮质素/皮质醇不平衡,DNA损伤反应增加
Şeyma Başar Kılıç1, Serpil Taheri2,3, Ecmel Mehmetbeyoğlu Duman3,4
1Dermatology and Venereology Department, Faculty of Medicine, Aksaray University, Aksaray, Turkey.
Molecular biology reports
|August 24, 2024
概括
牛皮会破坏皮肤屏障和免疫防御,与DNA损伤修复 (DDR) 有关. 这项研究揭示了类固醇激素路径的改变和牛皮的皮肤中的雄激素优势,这表明了这种慢性皮肤疾病的新治疗点.
科学领域:
- 皮肤病学 皮肤病学
- 遗传学 遗传学 是一个
- 内分泌学 在内分泌学.
背景情况:
- 牛皮涉及表皮屏障功能障碍,角质细胞异常和炎症.
- 由短端粒表示的基因毒性表明牛皮患者的免疫防御和DNA损伤修复 (DDR) 受到损害.
- DDR机械和激素信号通路之间的交叉声会影响疾病的进展和治疗反应.
研究的目的:
- 在牛皮皮肤发育期间调查类固醇生物合成和基因组稳定性标记物的并行改变.
- 为了了解类固醇途径与牛皮病原发生过程中的DNA损伤反应之间的相互作用.
主要方法:
- 来自牛皮患者和健康对照者的皮肤 (损伤和非损伤) 和血液样本的分析.
- 实时PCR测量雌激素受体 (ESR1,ESR2),雄激素受体 (AR),葡萄糖皮质体/矿物质皮质体受体 (NR3C1,NR3C2),类固醇酶 (HSD11B1/HSD11B2) 和DNA损伤传感器的转录水平.
主要成果:
- 与对照人群相比,病变牛皮皮肤中的ESR1,ESR2,HSD11B1,NR3C1,NR3C2,POLH和SMC1A转录显著下降.
- 在病变性牛皮皮肤中,AR,TREX1,RAD1和SSBP3转录的显著增加.
- 在损伤性牛皮组织中观察到的类固醇源途调节的破坏.
结论:
- 牛皮病变组织表现出乱的类固醇生成途径调节,与不足的葡萄糖皮质/矿物质皮质反应和改变的雌激素/雄激素平衡有利于雄激素.
- 增加的雄激素反应与DDR相结合可能会增加牛皮的风险.
- 这些发现表明,有可能针对新型治疗策略,针对类固醇生成和牛皮的DNA损伤反应之间的相互作用.
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