普罗托卡德林20通过向ATF6来维持肠道屏障功能,以保护克罗恩病
Shanshan Huang1, Zhuo Xie1, Jing Han1
1Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, 510080, Guangdong Province, People's Republic of China.
Genome biology
|July 5, 2023
概括
在克罗恩病中,Protocadherin 20 (PCDH20) 对于保持肠道屏障完整性至关重要. 它的下调会破坏肠道屏障功能,但激活ATF6可以恢复它.
科学领域:
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 肠道屏障功能障碍是克罗恩病发病的核心原因.
- 甲素20 (PCDH20) 是甲素超级家族的成员,被认为是克罗恩病的关键因素.
- 了解PCDH20在肠道平衡和屏障完整性中的作用至关重要.
研究的目的:
- 研究PCDH20在维持肠道平衡中的作用.
- 阐明PCDH20调节肠道屏障完整性的机制.
- 探索PCDH20在克罗恩病发展中的作用.
主要方法:
- 在患者和小鼠模型中对PCDH20mRNA和蛋白质表达的定量分析.
- 产生和分析肠道特异性Pcdh20淘汰小鼠.
- 在小鼠模型中使用DSS和TNBS诱导大肠炎.
- 研究附着体结交动力学和相关的蛋白质调节 (β-catenin,p120-catenin).
- 作为下游效应因子,对激活转录因子6 (ATF6) 的功能性评估.
主要成果:
- 在克罗恩氏病患者和结肠炎模型中,PCDH20表达显著下调.
- 肠道Pcdh20淘汰会导致肠细胞分化缺陷和障碍物完整性的破坏.
- 由于PCDH20缺乏,它会通过β-catenin和p120-catenin影响附着结,从而加剧结肠炎.
- 激活转录因子6 (ATF6) 被确定为PCDH20的下游效应因子.
- 在Pcdh20缺陷模型中,ATF6激活逆转了肠道屏障缺陷和通路失调.
结论:
- PCDH20对于维持肠上皮质平衡和屏障完整性至关重要.
- 通过通过ATF6/CHOP/β-catenin/p-p120-catenin通路加强粘附结,PCDH20可以保护大肠炎.
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