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DHX9通过抑制肠道干细胞中R环介导的基因组不稳定性来维持表皮平衡
Xingxing Ren1,2,3, Qiuyuan Liu4, Peirong Zhou3
1Hefei National Research Center for Physical Sciences at the Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230001, Hefei, China.
Nature communications
|April 9, 2024
概括
在炎症性肠病 (IBD) 中减少的DHX9蛋白质会损害肠道干细胞 (ISC). 缺少DHX9会导致R循环积累,基因组不稳定和炎症,使IBD恶化. 这突出了DHX9的亮点.
科学领域:
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 炎症性肠病 (IBD) 具有表皮屏障功能障碍和密室损伤的特征.
- 肠干细胞 (ISC) 对于肠上皮细胞 (IEC) 的更新和修复至关重要.
- 在IBD病原体中ISC失调的作用尚未完全理解.
研究的目的:
- 研究DHX9在肠干细胞功能和IBD中的作用.
- 阐明DHX9缺乏影响ISC恒温的分子机制.
- 确定DHX9作为IBD的潜在治疗点.
主要方法:
- 在IBD患者中分析DHX9蛋白水平.
- 产生和表征肠表皮特异性DHX9缺陷小鼠 (Dhx9ΔIEC).
- 评估ISC和帕内斯细胞数量,R循环积累,基因组不稳定性和cGAS-STING通路激活 in vivo和in vitro.
主要成果:
- 在IBD患者中观察到降低的DHX9蛋白水平.
- DHx9ΔIEC小鼠对实验性结肠炎的敏感性增加.
- 在ISC中DHX9缺乏导致R循环积累,基因组不稳定性,cGAS-STING介导的炎症和ISC功能受损.
结论:
- DHX9对于维持肠上皮质平衡和ISC功能至关重要.
- DHX9缺陷通过R循环积累和基因组不稳定性,有助于IBD病原体.
- 向DHX9或R环形成可能为IBD提供治疗策略.
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