WTAP促进性结肠炎的进展,通过沉默CES2的表达通过m6A修改
Xiaoran Xie1, Sha Cheng2, Xiong Chen2
1Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China; Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China; Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Jinan, Shandong, China.
通过m6A修饰,通过沉默CES2,影响免疫反应,WTAP促进性结肠炎 (UC). 针对WTAP提供了一个潜在的UC治疗策略.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
背景情况:
- 性结肠炎 (UC) 是一种慢性炎症性肠病.
- WTAP (威尔姆斯瘤1-关联蛋白) 在UC病原和免疫调节中的作用尚未完全理解.
研究的目的:
- 调查WTAP在UC中的功能.
- 在UC的背景下探索WTAP对免疫反应的调节.
- 阐明WTAP在UC进展中的作用背后的分子机制.
主要方法:
- 在UC组织中分析WTAP和CES2表达.
- 对巨细胞两极分化和T细胞透的评估.
- 检测m6A修饰,mRNA稳定性和蛋白质相互作用 (m6A-RIP-PCR,RIP,Co-IP,露西法酶试验).
- 使用UC小鼠模型和体外细胞培养系统的体内研究.
主要成果:
- 在UC组织中,WTAP表达升高,而CES2表达下降.
- 通过减少M1巨细胞极化和CD4+T细胞透,WTAP敲除改善了UC进展.
- 与YTHDF2复合的WTAP促进CES2mRNA的m6A修饰,导致其抑制.
- 过度表达CES2促进了肠道上皮细胞的分化,其敲除部分逆转了WTAP敲除的保护作用.
结论:
- 通过m6A修改,WTAP/YTHDF2复合物沉默了CES2,从而促进了UC的进展.
- WTAP代表了性结肠炎的潜在治疗标.
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