Colonic epithelial-derived FGF1 drives intestinal stem cell commitment toward goblet cells to suppress inflammatory bowel disease

IF 14.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-04-05 DOI:10.1038/s41467-025-58644-2

Qian Lin, Sudan Zhang, Jiaren Zhang, Yi Jin, Taoli Chen, Ruoyu Lin, Jiaxuan Lv, Wenjing Xu, Tianzhen Wu, Shenyu Tian, Lei Ying, Xiaokun Li, Zhifeng Huang, Jianlou Niu

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Abstract

Understanding the molecular mechanisms that regulate intestinal epithelial cell (IEC) renewal provides potential targets for inflammatory bowel disease (IBD). Growing evidence has highlighted the importance of epithelial signals in regulating intestinal stem cell (ISC) differentiation. However, it remains unclear which IEC-derived cytokines can precisely regulate ISC commitment toward specific mature cells. Here we systematically analyze all fibroblast growth factors (FGFs) expression and find that colonic FGF1 levels are inversely correlated with the severity of IBD in mouse models and patients. IEC-specific Fgf1 deletion leads to impaired goblet cell differentiation and exacerbated colitis, while pharmacological administration of recombinant FGF1 (rFGF1) alleviates colitis by enhancing goblet cell differentiation and improving colonic epithelial integrity. Mechanistic studies reveal that rFGF1 directs ISC differentiation toward goblet cells via FGFR2-TCF4-ATOH1 signaling axis. In conclusion, our study identifies an epithelial niche-derived FGF1 that regulates ISC commitment toward goblet cells, shedding light on strategies for treating IBD.

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结肠上皮源性 FGF1 推动肠干细胞向上皮细胞承诺，从而抑制炎症性肠病

了解调节肠上皮细胞（IEC）更新的分子机制为炎症性肠病（IBD）提供了潜在的靶点。越来越多的证据强调了上皮信号在调节肠干细胞（ISC）分化中的重要性。然而，目前尚不清楚哪些iec衍生的细胞因子可以精确地调节ISC对特定成熟细胞的承诺。在这里，我们系统地分析了所有成纤维细胞生长因子（FGF1）的表达，发现在小鼠模型和患者中，结肠FGF1水平与IBD的严重程度呈负相关。iec特异性Fgf1缺失导致杯状细胞分化受损和结肠炎加重，而重组Fgf1 （rFGF1）的药理学管理通过增强杯状细胞分化和改善结肠上皮完整性来缓解结肠炎。机制研究表明，rFGF1通过FGFR2-TCF4-ATOH1信号轴引导ISC向杯状细胞分化。总之，我们的研究确定了一种上皮小生境衍生的FGF1，它调节ISC对杯状细胞的承诺，为治疗IBD的策略提供了线索。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.