葡萄糖感应ChREBP蛋白在糖尿病视网膜病变的发病过程中
Christopher R Starr1, Assylbek Zhylkibayev2, Oleg Gorbatyuk3
1University of Alabama at Birmingham, School of Medicine, Department of Ophthalmology.
bioRxiv : the preprint server for biology
|December 16, 2024
概括
葡萄糖感应的ChREBP和MondoA转录因子与糖尿病视网膜病变 (DR) 有关. 在小鼠中,ChREBP的过度表达重新编程了视网膜代谢,导致功能损失和光感应器退化,突出了其在DR病变发生中的作用.
科学领域:
- 眼科医生 眼科 眼科
- 代谢研究研究 代谢研究
- 分子生物学分子生物学
背景情况:
- 葡萄糖感应转录因子ChREBP和MondoA是代谢途径的关键调节者.
- 它们在眼部疾病,特别是糖尿病视网膜病变 (DR) 中所起的作用仍未得到充分研究.
- ChREBP和MondoA与代谢障碍相关的脂质,炎症和胰岛素信号通路有关.
研究的目的:
- 调查转录因子ChREBP在糖尿病视网膜病变 (DR) 病变发生过程中的作用.
- 探索ChREBP过度表达对视网膜功能和新陈代谢的影响.
主要方法:
- 人类和小鼠视网膜冷切割的免疫组织化学.
- 定量实时PCR (qRT-PCR) 用于基因表达分析.
- 用于视网膜功能测试和蛋白质组分析 (LC-MS) 的构成性活跃ChREBP (caChREBP) 表达小鼠 (caChREBPRP) 的生成.
- 全球ARPE-19细胞的蛋白质组设计以表达人类ChREBP (ARPE-19ChREBP).
主要成果:
- ChREBP和MondoA在视网膜中表达,ChREBP分布广泛,而MondoA在体中突出.
- 在DR中,ChREBP和MondoA表达都被提升了.
- 在caChREBPRP小鼠中,可图电网红图 (ERG) 幅度降低,表明杆光感受器功能障碍.
- 视网膜蛋白质组分析显示,与光传导,氨基酸代谢和细胞粘附相关的KEGG通路减少.
- 棒特异性ca-ChREBP诱导的TXNIP表达. 棒特异性ca-ChREBP诱导的TXNIP表达.
- ARPE-19ChREBP细胞表现出新陈代谢重编程,包括增加氧酸盐信号传递,糖代谢和 lysosomal激活.
结论:
- 过度表达ChREBP显著重编程视网膜代谢.
- 这种代谢重编程会触发视网膜中的功能损失和光受体退化.
- 在糖尿病视网膜病变的发病过程中,ChREBP起着至关重要的作用.
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