BCAT1激活重编程分支链氨基酸代谢,并在表观遗传学上促进糖尿病视网膜病变的炎症

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Jingyi Wang^1,2,3, Zihan Yin^1,2,3, Jingxiao Yang^2,3

¹Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, National Clinical Key Specialty Construction Project, Shanghai, China.

Investigative ophthalmology & visual science

|June 18, 2025

概括

分支链氨基酸 (BCAA) 代谢在Müller细胞中由Bcat1重塑,在表观遗传上驱动糖尿病视网膜病变. 抑制Bcat1可减少视网膜炎症和血管泄漏,提供了一个新的治疗点.

科学领域:

眼科医生眼科眼科
代谢研究研究代谢研究
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.

背景情况:

糖尿病视网膜病变 (DR) 是导致视力丧失的主要原因.
氨基酸代谢在DR病变发生中的作用尚未完全理解.
分支链氨基酸 (BCAA) 代谢变化可能会导致DR.

研究的目的:

为了研究BCAA代谢在糖尿病视网膜病变中的重塑.
为了确定BCAA代谢对DR进展的贡献.
确定Bcat1作为DR的潜在治疗点.

主要方法:

在视网膜单细胞测序数据中分析了Bcat1和Bcat2表达.
使用代谢学评估了Müller细胞中的Bcat1活性.
通过ChIP检查了通过RNA测序的基因表达和通过基因表达的组分子甲基化.
利用酶选试验和糖尿病小鼠模型与Bcat1抑制剂.

主要成果:

Bcat1,主要在米勒细胞中,在糖尿病中调高了炎症基因 (Il6,Tnf-α).
通过Plk4酸化调节的Bcat1活性,降低了α-KG,增加了炎症促进者的H3K4me3.
在体内,BCAT1抑制显著降低了视网膜炎症和血管泄漏.

结论:

在DR中,Bcat1激活通过BCAA新陈代谢重塑来表观遗传诱导视网膜炎症.
Bcat1代表了糖尿病视网膜病变的潜在治疗标.
不调节的氨基酸代谢,以及高血糖症,可能会导致糖尿病和DR.

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