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在大肠炎中,IGF2BP2通过稳定m6的A-修改GPX4mRNA来减弱肠上皮细胞铁

Wei Liu¹, Hui Zeng¹

¹Department of Pediatric Gastroenterology, Children's Hospital of The First People's Hospital of Chenzhou City, Chenzhou 423000, Hunan Province, PR China.

|December 1, 2023

概括

胰岛素样生长因子2mRNA结合蛋白2 (IGF2BP2) 通过通过m6A修饰增强GPX4表达来抑制性结肠炎 (UC) 的进展,从而减少铁亡.

科学领域:

分子生物学分子生物学
胃肠病学胃肠病学
免疫学免疫学免疫学

背景情况:

性结肠炎 (UC) 是一种慢性炎症性肠病,对其分子机制的理解有限.
N6 - 甲基氨酸 (m6A) 修饰在调节基因表达中起作用.
在UC病变发生过程中,m⁶A相关蛋白质 (例如IGF2BP2) 的功能在很大程度上是未知的.

研究的目的:

研究IGF2BP2在性结肠炎的作用和潜在机制.
分析IGF2BP2,m⁶A修饰和UC中的ferroptosis之间的关系.

主要方法:

在细胞系和小鼠中使用硫酸 (DSS) 的已建立的UC模型.
量化IGF2BP2和GPX4的表达通过qPCR和西布洛特.
进行了功能增益和丧失实验,以评估IGF2BP2对炎症,铁亡和结肠损伤的影响.
使用m6ARNA甲基化量化,RNA免疫沉-qPCR和RNA稳定性试验来阐明分子机制.

主要成果:

在DSS诱导的UC中,IGF2BP2和GPX4的下调.
IGF2BP2过度表达减少了活性氧物种 (ROS),MDA和铁水平,同时增加了细胞中的GSH和GPX4水平.
在UC小鼠中,IGF2BP2过度表达改善了疾病活动,炎症和铁亡.
发现IGF2BP2通过m⁶A修改来增强GPX4mRNA的稳定性.

结论:

IGF2BP2在性结肠炎中起着保护作用.
IGF2BP2通过m6A修改增加了GPX4表达,从而抑制了ferroptosis并减轻了UC的进展.

关键词:

铁化是铁化的一种.在GPX4中使用GPX4.在IGF2BP2BP2中使用.M(6) 一种mRNA修饰.性结肠炎是一种

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