FGF1ΔHBS通过减少通过MAPK通路的中性粒细胞招募来改善DSS诱导的性结肠炎
Shuang Feng1,2,3,4, Yanyan Jin2,3,4, Xinrui Ni2,3,4
1Institute of Translational Medicine, China Pharmaceutical University, Nanjing, China.
British journal of pharmacology
|April 21, 2025
概括
纤维细胞生长因子1 (FGF1) 变体FGF1有效地治疗小鼠的大肠炎,通过抑制MAPK通路减少炎症和中性粒细胞的招募. 这为炎症性肠道疾病 (IBD) 提供了潜在的新疗法.
科学领域:
- 胃肠道学和免疫学
- 分子生物学和信号通路
背景情况:
- 炎症性肠病 (IBD) 是一种慢性胃肠道疾病,其全球发病率正在增加.
- 目前用于IBD的治疗方法缺乏足够的疗效和安全性,这突显了需要新的治疗方法的需要.
- 纤维细胞生长因子1 (FGF1) 变异FGF1ΔHBS在其他炎症状况中显示出治疗前景.
研究的目的:
- 在大肠炎的小鼠模型中研究FGF1ΔHBS的治疗潜力.
- 阐明FGF1ΔHBS发挥其保护作用的潜在分子机制.
主要方法:
- 在小鼠中使用硫酸 (DSS) 诱导的大肠炎模型来评估FGF1ΔHBS的疗效.
- RNA测序 (RNA-seq) 分析了结肠组织的基因表达.
- 定量实时PCR,ELISA,流细胞测量,免疫光和西部斑点检测评估了炎症标志物,中性粒细胞的招募和MAPK信号通路的激活.
主要成果:
- 在DSS诱导的大肠炎中,FGF1显著降低了疾病活性和结肠组织学损伤.
- 用FGF1ΔHBS治疗导致促炎因素的表达减少.
- FGF1ΔHBS抑制了MAPK信号通路,抑制了与中性粒细胞相关的化学基因表达和随后的中性粒细胞招募.
结论:
- 在小鼠中,FGF1ΔHBS显示出对DSS诱导的大肠炎的显著保护作用.
- 该机制涉及通过抑制MAPK信号通路来抑制中性粒细胞的招募.
- FGF1ΔHBS代表了一个有希望的治疗候选人,用于管理炎症性肠道疾病.
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