结肠表皮衍生的FGF1驱动肠干细胞对杯细胞的承诺,以抑制炎症性肠病
Qian Lin1, Sudan Zhang1, Jiaren Zhang1
1State Key Laboratory of Macromolecular Drugs and Large-scale Preparation, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Nature communications
|April 5, 2025
概括
来自肠道上皮细胞的纤维细胞生长因子1 (FGF1) 促进了杯状细胞的分化. 通过增强上皮质修复和杯状细胞再生,FGF1的使用可缓解炎症性肠病 (IBD).
科学领域:
- 分子生物学分子生物学
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
背景情况:
- 肠上皮细胞 (IEC) 更新对肠道健康至关重要,也是炎症性肠病 (IBD) 的潜在目标.
- 表皮信号调节肠干细胞 (ISC) 的分化,但控制ISC承诺的特定IEC衍生细胞因子在很大程度上是未知的.
研究的目的:
- 研究纤维细胞生长因子 (FGFs) 在调节ISC分化中的作用及其作为IBD治疗点的潜力.
- 阐明FGF1影响杯状细胞分化和肠上皮质完整性的特定机制.
主要方法:
- 在IBD模型和患者中对FGF表达的系统分析.
- 产生IEC特定的Fgf1淘汰小鼠.
- 将复合FGF1 (rFGF1) 给大肠炎的小鼠模型.
- 涉及FGFR2-TCF4-ATOH1信号通路分析的机制研究.
主要成果:
- 结肠FGF1水平与小鼠和患者的IBD严重程度有负相关性.
- 特定于IEC的Fgf1删除会加剧结肠炎并损害小杯细胞分化.
- rFGF1治疗通过促进杯状细胞分化和恢复上皮质完整性来改善结肠炎.
- FGF1通过FGFR2-TCF4-ATOH1信号轴作用,以直接将ISC分化转向杯状细胞.
结论:
- 表皮基衍生的FGF1是ISC致力于杯状细胞系的关键调节者.
- 通过增强杯状细胞再生和上皮细胞修复,FGF1代表了IBD的一个有前途的治疗标.
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