在小鼠中,通过肠上皮质IL-22-STAT3激活,FGF21的耗尽减轻结肠炎
Liming Liu1,2, Fengyuan Li2,3, Tuo Shao2
1College of Animal Science and Technology, Jilin Agricultural Science and Technology University, Jilin 132101, China.
Nutrients
|July 11, 2023
概括
纤维细胞生长因子21 (FGF21) 缺陷对小鼠的炎症性肠病 (IBD) 进行保护. 淘汰FGF21的小鼠显示大肠炎的严重程度和炎症减少,这表明FGF21阻断是潜在的IBD治疗策略.
科学领域:
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
背景情况:
- 纤维细胞生长因子21 (FGF21) 调节新陈代谢,并由炎症诱导.
- 在炎症性肠病 (IBD) 中FGF21的作用仍然未被探索.
- IBD的特点是胃肠道的慢性炎症.
研究的目的:
- 为了研究FGF21在硫酸 (DSS) 诱导的急性结肠炎中的作用,IBD的实验模型.
- 确定FGF21缺乏对结肠炎严重程度和相关炎症反应的影响.
- 阐明FGF21影响肠道炎症的潜在分子机制.
主要方法:
- 在FGF21淘汰赛 (KO) 和野生型 (WT) 小鼠中使用DSS管理建立了一个实验性IBD模型.
- 评估了结肠炎的严重程度,体重减轻和结肠组织炎症.
- 分析了血和结肠中的促炎因素水平,细胞增殖 (BrdU染色) 和特定细胞群 (Paneth和杯细胞).
- 机制研究涉及评估信号传感器和转录激活器 (STAT) -3激活,IL-22表达和细胞因子信号传导抑制剂 (SOCS) 2/3表达在肠上皮细胞中.
主要成果:
- 用DSS治疗的WT小鼠表现出高血FGF21,显著的体重减轻和严重的结肠炎.
- 与WT小鼠相比,FGF21 KO小鼠的体重减轻显著,大肠炎的严重程度降低.
- 缺乏FGF21导致了较低的促炎因素,增加了结肠上皮细胞的增殖,并保持了帕内斯和杯状细胞的数量.
- 从机制上讲,FGF21缺乏增强了STAT3激活和IL-22表达,同时抑制了肠上皮细胞中的SOCS 2/3.
结论:
- 在小鼠中,FGF21缺乏改善了DSS诱导的急性结肠炎.
- 这种保护作用与肠道上皮细胞中增强的IL-22-STAT3信号传递有关.
- 这些发现表明FGF21是IBD的潜在治疗点.
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