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通过Keap1/Nrf2信号传递,ON101可以抵消辐射引起的皮肤炎中的氧化应激和炎症
Yi-Chieh Tsai1, Ming-Shou Hsieh2, Iat-Hang Fong2
1Department of Radiation Oncology, Taipei Medical University - Shuang Ho Hospital, New Taipei City 23561, Taiwan.
通过减少皮肤损伤和炎症,ON101有效治疗辐射诱导性皮肤炎 (RID). 这种局部治疗激活了Keap1/Nrf2通路,促进了抗氧化反应和对辐射皮肤毒性的组织修复.
科学领域:
- 皮肤病学 皮肤病学
- 分子生物学分子生物学
- 放射治疗研究 放射治疗研究
背景情况:
- 辐射诱导性皮肤炎 (RID) 是一种常见的,具有挑战性的放射治疗副作用,局部治疗有限.
- 凯普1/Nrf2信号通路对于细胞防御氧化应激至关重要.
研究的目的:
- 研究ON101在治疗辐射诱导性皮肤炎 (RID) 的疗效和作用机制.
- 评估ON101对Keap1/Nrf2通路及其抗氧化和抗炎作用的影响.
主要方法:
- 用于评估局部ON101治疗的辐射诱导皮肤损伤的小鼠模型.
- 进行了组织学分析 (H&E,马森三色) 和RNA测序.
- 在人体角质细胞 (HaCaT) 和皮肤纤维细胞 (HDF) 的体外研究评估了氧化应激和炎症标志物.
主要成果:
- 在小鼠模型中,ON101显著减少了皮肤损伤,改善了组织病理学,并保持了体重.
- 在体外,ON101降低了Keap1,激活了Nrf2,并降低了氧化应激和炎症标志物.
- 治疗促进了DNA修复和皮肤再生基因 (EGFR,VIM,CTNNB1) 的表达,并激活了p62-Keap1-Nrf2轴.
结论:
- 通过调节氧化应激,炎症和促进组织修复,ON101证明了对辐射诱导皮肤炎的全面保护.
- ON101激活Keap1/Nrf2通路是其治疗效果的一个关键机制.
- ON101是一种有前途的局部药物,用于控制辐射引起的皮肤毒性.
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