隔膜细胞骨架是肠上皮质屏障完整性和粘膜炎症的调节者
Nayden G Naydenov1, Gaizun Hu2,3, Dominik Robak2,3
1Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
JCI insight
|October 7, 2025
概括
九月蛋白 (SEPT9) 通过定结节蛋白来维持肠道屏障的完整性至关重要. SEPT9功能障碍有助于炎症性肠病 (IBD) 和漏肠,突出其保护作用.
科学领域:
- 细胞生物学 细胞生物学
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
背景情况:
- 肠上皮质屏障的完整性对健康至关重要,其破坏与炎症性疾病有关.
- 细胞骨蛋白家族的septins在肠道屏障功能中的作用仍然在很大程度上未被探索.
- 七月9号 (SEPT9) 功能障碍与肠道病理有关,这表明它可能在肠道健康方面发挥作用.
研究的目的:
- 为了研究 Septin 9 (SEPT9) 在维护肠道上皮质屏障完整性的作用.
- 阐明SEPT9影响肠道屏障功能的分子机制.
- 评估SEPT9在炎症性肠病 (IBD) 的背景下的重要性.
主要方法:
- 在肠道上皮细胞 (IECs) 中对SEPT9的定位研究.
- 在小鼠模型中进行IEC特定的SEPT9移除,以评估屏障功能和结肠炎易感性.
- 亲和净化质谱和超分辨率成像以识别SEPT9交互伙伴.
- 在人类IBD患者样本中分析SEPT9表达.
主要成果:
- 在IEC中,SEPT9定位在顶端结点 (紧密并粘附结点) 上.
- 在小鼠中,SEPT9 除导致"漏肠"表型,并增加对实验性结肠炎的易感性.
- SEPT9与非肌肉肌肉蛋白IIC (NMIIC) 相互作用,并被要求将其招募到环节性动肌蛋白皮带中,这对于屏障完整性至关重要.
- 在IBD患者的肠道粘膜中观察到SEPT9表达的减少.
结论:
- 通过NMIIC招募,SEPT9对于调节肠道屏障完整性至关重要,它通过NMIIC招募支持结合复合组合.
- 隔膜细胞骨架,特别是SEPT9,在炎症期间在肠道粘膜中起着关键的保护作用.
- 在IBD中,SEPT9功能障碍和减少表达表明这种保护机制的丧失,有助于疾病的发病.
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