激活的痕信号通路通过调节紧密的结节来保护DSS诱导的大肠炎中的肠壁
Tingting Li1,2, Chong Geng3, Xiao Li2
1Department of Gastroenterology, First Affiliated Hospital of Soochow University, Suzhou, China.
European journal of medical research
|January 22, 2026
概括
诺奇通路通过调节紧密结 (TJ) 和肌酸酶轻链激酶 (MLCK) 路径来保护肠道屏障. 激活Jag1/Notch1/Hes1信号,可以防止炎症损伤和TJ功能障碍.
科学领域:
- 胃肠病学 胃肠病学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 诺奇通路在保护肠粘膜屏障中的作用已被建议,但尚未完全理解.
- 阐明分子机制对于理解炎症性肠道疾病至关重要.
研究的目的:
- 为了研究Notch通路激活在肠粘膜屏障上的保护机制.
- 为了确定 Notch 信号,紧密连接和 MLCK 路径之间的关系.
主要方法:
- 使用硫酸 (DSS) 诱导的大肠炎小鼠模型和Caco-2细胞培养物.
- 抑制了诺奇与LY411,575的信号,并通过Hes1过度表达激活了它.
- 分析了紧密结合完整性和肌轻链激酶 (MLCK) 路径激活.
- 在TNF-α处理的Caco-2细胞中研究了Notch配体和受体.
主要成果:
- 切口抑制导致大肠炎恶化,TJ恶化和MLCK活化 in vivo.
- 在体外,诺奇信号调节了TJ功能;MLK抑制 (ML-7) 改善了LY411,575诱导的TJ功能障碍.
- TNF-α增加了Jag1,Notch1和Hes1的表达;Jag1的沉默降低了NICD1和Hes1.1.
结论:
- 该Jag1/Notch1/Hes1信号通路保护肠道粘膜屏障免受炎症损伤.
- 这种保护是通过防止依赖于MLCK的紧结失调来实现的.
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