由结肠杯状细胞产生的IgGFc结合蛋白和MUC2粘素在空间上非共价相互作用,调节伤口愈合
Hayley Gorman1,2, France Moreau1,2, Antoine Dufour3,4
1Department of Microbiology, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada.
该研究表明,MUC2粘素和FCGBP (IgGFc结合蛋白) 通过甘氨酸相互作用,影响粘液结构和上皮屏障功能. 缺少MUC2可以加速伤口愈合,这表明FCGBPP.
科学领域:
- 胃肠道学和免疫学
- 皮质生物学 皮质生物学
- 粘膜免疫学 粘膜免疫学
背景情况:
- 结肠粘液层对于宿主防御和微生物群平衡至关重要.
- MUC2粘液和FCGBP (IgGFc结合蛋白) 是结肠粘液的关键组成部分.
- 了解它们的相互作用对于上皮质屏障功能至关重要.
研究的目的:
- 研究MUC2粘素和FCGBP的生物合成和相互作用.
- 确定它们在分泌粘液的结构完整性中的联合作用.
- 阐明它们在上皮屏障修复中的功能.
主要方法:
- 在杯状细胞中的协同表达分析.
- 在CRISPR-Cas9基因编辑中创建MUC2淘汰 (KO) 细胞.
- 协焦显微镜用于同位化研究.
- STRING-db v11 分析粘素颗粒蛋白质组.
- 在体内伤口愈合和DSS结肠炎模型.
主要成果:
- MUC2和FCGBP是协调调节的,并在粘素颗粒中同位化,但FCGBP也显示了扩散的细胞质分布.
- 在分泌的粘液中,FCGBP通过N结合的甘氨酸与MUC2相互作用,并且非共价.
- 在KO细胞中缺少MUC2会导致细胞质FCGBP增加,并加速伤口愈合.
- 在WT细胞中,伤口边缘的MUC2和FCGBP两极分化阻碍了关闭.
- 在MUC2KO小鼠中,DSS结肠炎显示FcgbpmRNA增加和蛋白质表达延迟,这表明它具有保护作用.
结论:
- MUC2和FCGBP相互作用,保持粘液结构和上皮屏障完整性.
- FCGBP在伤口愈合中的作用是复杂的,并取决于MUC2的存在.
- FCGBP可能在结肠伤口愈合和屏障功能中发挥内源性保护作用,特别是在炎症期间.
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