BACKGROUND In liver cirrhosis, intestinal mucus barrier is rarely studied. AIMS This study aimed to investigate whether mucus barrier in ileum is altered in cirrhotic rats and its underlying mechanisms. METHODS Thioacetamide was injected to induce liver cirrhosis in rats. Serum from portal vein blood, and ileum and liver tissues were obtained for further analysis. Goblet cell-like Ls174T cells were cultured for in vitro experiments. RESULTS The ileal mucus was thin, loose, and porous with small bubbles in cirrhotic rats. mRNA expressions of Muc2 and TFF3 were also down-regulated in cirrhotic rats. Bacteria located near to crypts and LPS were increased in the serum from portal vein in cirrhotic rats. Smaller theca area and few goblet cells were found in cirrhotic rats compared with control. Increased proliferation of ileal epithelia was observed in cirrhotic rats. Notch1, Dll1, and Hes1 expressions were enhanced, and KLF4 expression was suppressed in ileum of cirrhotic rats. In Ls174T cells, EDTA and NICD plasmid induced NICD and Hes1 expression and suppressed KLF4 concomitantly, and mucus expression almost vanished in these cells. NICD plasmid induced more proliferation in Ls174T cells. Oppositely, after DBZ treatment, NICD and Hes1 were inhibited along with augmentation of KLF4 and increased mucous expression in Ls174T cells, while proliferation of the cells was suppressed. CONCLUSIONS In cirrhotic rats, mucus barrier was impaired. This might be attributed to increased proliferation and decreased differentiation of epithelia, which might be mediated by Notch1-Hes1-KLF4 signaling.

中文翻译：

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肝硬化大鼠中Notch1信号传导引起的上皮稳态障碍导致的回肠粘液屏障受损。

背景技术在肝硬化中，很少研究肠粘液屏障。目的本研究旨在研究肝硬化大鼠回肠粘液屏障是否发生改变及其潜在机制。方法注射硫代乙酰胺诱导大鼠肝硬化。从门静脉血，回肠和肝组织中获取血清以进行进一步分析。培养杯状细胞样Ls174T细胞用于体外实验。结果肝硬化大鼠回肠粘液稀薄，疏松且有小气泡。肝硬化大鼠中Muc2和TFF3的mRNA表达也下调。肝硬化大鼠门静脉血清中位于隐窝和LPS附近的细菌增加。与对照组相比，肝硬化大鼠的鞘膜面积较小，杯状细胞很少。在肝硬化大鼠中观察到回肠上皮细胞增殖增加。肝硬化大鼠回肠中Notch1，Dll1和Hes1的表达增强，而KLF4的表达受到抑制。在Ls174T细胞中，EDTA和NICD质粒诱导NICD和Hes1表达并同时抑制KLF4，并且这些细胞中的粘液表达几乎消失。NICD质粒在Ls174T细胞中诱导更多增殖。相反，DBZ处理后，LCD174T细胞中NICD和Hes1随KLF4的增加和粘液表达的增加而受到抑制，而细胞的增殖受到抑制。结论在肝硬化大鼠中，粘液屏障受损。这可能归因于上皮细胞的增殖增加和分化减少，这可能是由Notch1-Hes1-KLF4信号传导介导的。肝硬化大鼠回肠中Hes1和Hes1表达增强，KLF4表达受到抑制。在Ls174T细胞中，EDTA和NICD质粒诱导NICD和Hes1表达，并同时抑制KLF4，在这些细胞中粘液表达几乎消失。NICD质粒在Ls174T细胞中诱导更多增殖。相反，DBZ处理后，LCD174T细胞中NICD和Hes1随KLF4的增加和粘液表达的增加而受到抑制，而细胞的增殖受到抑制。结论在肝硬化大鼠中，粘液屏障受损。这可能归因于上皮细胞的增殖增加和分化减少，这可能是由Notch1-Hes1-KLF4信号传导介导的。肝硬化大鼠回肠中Hes1和Hes1表达增强，KLF4表达受到抑制。在Ls174T细胞中，EDTA和NICD质粒诱导NICD和Hes1表达，并同时抑制KLF4，在这些细胞中粘液表达几乎消失。NICD质粒在Ls174T细胞中诱导更多增殖。相反，DBZ处理后，LCD174T细胞中NICD和Hes1随KLF4的增加和粘液表达的增加而受到抑制，而细胞的增殖受到抑制。结论在肝硬化大鼠中，粘液屏障受损。这可能归因于上皮细胞的增殖增加和分化减少，这可能是由Notch1-Hes1-KLF4信号传导介导的。EDTA和NICD质粒诱导NICD和Hes1表达并同时抑制KLF4，在这些细胞中粘液表达几乎消失。NICD质粒在Ls174T细胞中诱导更多增殖。相反，DBZ处理后，LCD174T细胞中NICD和Hes1随KLF4的增加和粘液表达的增加而受到抑制，而细胞的增殖受到抑制。结论在肝硬化大鼠中，粘液屏障受损。这可能归因于上皮细胞的增殖增加和分化减少，这可能是由Notch1-Hes1-KLF4信号传导介导的。EDTA和NICD质粒诱导NICD和Hes1表达并同时抑制KLF4，在这些细胞中粘液表达几乎消失。NICD质粒在Ls174T细胞中诱导更多增殖。相反，DBZ处理后，LCD174T细胞中NICD和Hes1随KLF4的增加和粘液表达的增加而受到抑制，而细胞的增殖受到抑制。结论在肝硬化大鼠中，粘液屏障受损。这可能归因于上皮细胞的增殖增加和分化减少，这可能是由Notch1-Hes1-KLF4信号传导介导的。在Ls174T细胞中，NICD和Hes1随KLF4的增加和粘液表达的增加而受到抑制，而细胞的增殖受到抑制。结论在肝硬化大鼠中，粘液屏障受损。这可能归因于上皮细胞的增殖增加和分化减少，这可能是由Notch1-Hes1-KLF4信号传导介导的。在Ls174T细胞中，NICD和Hes1随KLF4的增加和粘液表达的增加而受到抑制，而细胞的增殖受到抑制。结论在肝硬化大鼠中，粘液屏障受损。这可能归因于上皮细胞的增殖增加和分化减少，这可能是由Notch1-Hes1-KLF4信号传导介导的。