JAG1/Notch路径抑制诱导铁亡并促进白内障发生
Yan Ni1,2, Liangping Liu1,2, Fanying Jiang1,2
1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China.
International journal of molecular sciences
|January 11, 2025
概括
降低Notch信号的调节促进了透镜上皮细胞中的铁亡,导致与年龄相关的白内障. 增强Notch信号可能通过保护细胞死亡,为白内障提供治疗策略.
科学领域:
- 眼科医生 眼科 眼科
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 与年龄相关的白内障 (ARCs) 是全球视力障碍的主要原因.
- 驱动ARC病变的分子机制,特别是涉及细胞死亡途径,仍然不完全理解.
- 诺奇信号通路在退行性疾病中的作用表明,它可能与ARC有关.
研究的目的:
- 研究Notch信号在调节镜片上皮细胞 (LECs) 中铁亡的作用.
- 为了确定Notch信号对与年龄相关的白内障进展的影响.
- 阐明诺奇信号传递,铁灭菌和ARC发育之间的分子联系.
主要方法:
- 从ARC患者的前置透镜囊样本的RNA测序.
- 与年龄相关的Notch1表达和铁亡标记物的分析.
- 在体外实验中操纵LEC中的Notch信号,以评估铁亡标志物 (FTH1,p53,Nrf2,GPX4,SLC7A11) 的实验.
主要成果:
- ARC患者显示了下调的Notch信号和上调的铁灭菌标志物,与年龄相关的趋势.
- 在试验室中,Upregulating Notch信号通过降低FTH1/p53和增加Nrf2/GPX4/SLC7A11减少了铁亡.
- 抑制Notch信号加剧了铁亡,由减少的Nrf2/GPX4/SLC7A11表示.
结论:
- 降低Notch信号的调节,通过损害Nrf2/GPX4抗氧化途径,促进LEC中的铁亡.
- 这种Notch信号介导的铁致死有助于与年龄相关的白内障的发展.
- 诺奇信号通路代表了预防或治疗ARC的潜在治疗目标.
相关概念视频
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