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通过消除TNIP1的m6A甲基化,FTO推动了与炎症相关的糖尿病诱导的血管内皮功能障碍

Chuandi Zhou¹, Xinping She¹, Chufeng Gu¹

¹Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, 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 Diseases, Shanghai, China.

The Journal of clinical investigation

|October 2, 2023

概括

脂肪质量和与肥胖相关的蛋白质 (FTO) 调节糖尿病患者的内皮功能障碍. 准FTO-TNIP1-NF-κB通路可以治疗糖尿病血管并发症.

科学领域:

分子生物学分子生物学
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
血管生物学血管生物学

背景情况:

内皮功能障碍是糖尿病血管并发症的关键因素.
表观遗传修饰,包括N6-甲基氨酸 (m6A),调节内皮功能障碍中的炎症.
脂肪质量和与肥胖相关的蛋白质 (FTO) 是一个m6A脱甲基酶.

研究的目的:

研究FTO在糖尿病引起的血管内皮功能障碍中的作用.
在这种情况下,确定FTO的下游目标和机制.
探索针对糖尿病血管并发症的FTO途径的治疗潜力.

主要方法:

研究了FTO对内皮细胞 (EC) 和糖尿病小鼠模型的影响.
使用甲基化RNA免疫沉降测序 (MeRIP-Seq) 和RNA-Seq.
进行了 luciferase 活性测定和 RNA 下拉实验.
研究了TNIP1调节对炎症通路和血管完整性的影响.

主要成果:

增强的FTO降低了高血糖的全球m6A水平.
在EC中,FTO Knockdown降低了炎症,改善了细胞迁移和管道形成.
糖尿病小鼠的EC特异性FTO缺陷减少了视网膜血管泄漏和非细胞毛细血管的形成.
发现FTO通过去甲基化m6A.抑制TNIP1mRNA表达.
通过NF-κB通路,TNIP1枯竭加剧了内皮质损伤,而其持续表达缓解了内皮质损伤.

结论:

在糖尿病引起的内皮功能障碍中,FTO充当了表皮转录体调节剂.
FTO-TNIP1-NF-κB信号网络与糖尿病血管并发症有关.
针对FTO-TNIP1-NF-κB通路为糖尿病血管并发症提供了潜在的治疗策略.

关键词:

糖尿病糖尿病糖尿病内皮细胞是内皮细胞.表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.炎症炎症是一种炎症.血管生物学血管生物学

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