由于FTO缺乏而破坏CerS6介导的脂代谢,使性结肠炎恶化
Yanru Ma1, Xinyu Zhang1, Baoqin Xuan1
1State Key Laboratory of Systems Medicine for Cancer; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Division of Gastroenterology and Hepatology; Shanghai Cancer Institute; Shanghai Institute of Digestive Disease; Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Gut
|September 21, 2023
概括
脂肪质量和肥胖相关蛋白 (FTO) 在肠上皮细胞的下调促进性结肠炎 (UC) 通过增加素-1-酸盐 (S1P) 积累. 在UC患者中,较低的FTO表达可能预示着对vedolizumab治疗的更好的反应.
科学领域:
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 在肠上皮细胞 (IECs) 中RNA N6-甲基氨酸 (m6A) 修饰的放缓与肠炎症有关.
- 研究了m6A脱甲基酶脂肪质量和肥胖相关蛋白 (FTO) 在性结肠炎 (UC) 中的作用.
研究的目的:
- 在UC的背景下调查FTO的功能.
- 探索FTO影响肠道炎症的分子机制.
主要方法:
- 来自Fto缺乏小鼠和人类UC队伍的结肠组织的分析.
- 实时PCR,16s rRNA测序,RNA和甲基化RNA免疫沉降测序.
- 在体外研究涉及巨细胞和IECs,液体染色学-质谱仪用于胺的识别.
主要成果:
- 在UC患者和用硫酸 (DSS) 治疗的Fto缺乏小鼠中观察到FTO下调.
- 缺少FTO导致肠道失调,增加了促炎性巨细胞,并增强了Th17细胞分化.
- FTO缺陷增加了m6A的修饰,降低了CerS6mRNA的稳定性,并导致IEC中的S1P积累,随后促进大肠炎.
结论:
- 通过m6A-依赖机制,FTO下调会通过降低CerS6表达和增加S1P积累来加剧UC.
- 在UC患者中较低的FTO表达可能表明对vedolizumab治疗的良好反应.
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