Background

The intestinal mechanical barrier plays a key role in the pathogenesis of ulcerative colitis (UC). Our previous study showed keratin 1 (KRT1) was downregulated in UC, but the mechanism by which KRT1 affects the intestinal barrier remains unknown.

Objectives

To explore the mechanism of KRT1 in the intestinal barrier in UC.

Methods

Colonic tissues were collected from 20 UC patients before and after mucosal healing (MH) and 15 healthy controls. The expression of KRT1 was measured by PCR, western blotting and immunohistochemistry (IHC). A dextran sulfate sodium (DSS)-induced colitis model was established in krt1 transgenic (TG) mice, and the mice were treated with methylprednisolone (MP) to explore the role of KRT1 in the intestinal barrier. Inflammation was evaluated through the DAI score, colon, spleen and H&E. The expression of KRT1 and tight junction (TJ) proteins in mouse was analysed by the same methods.

Results

The transcription and expression of KRT1 in UC was decreased and recovered after MH but did not reach the level of the healthy controls. Similar to the clinical results, the expression of krt1 was decreased in DSS-induced colitis and upregulated after MP. Moreover, the krt1 TG group exhibited less inflammation than wild-type (WT) group. The expression of Occludin and ZO-1 decreased after DSS induction, the decreases in Occludin and ZO-1 in the krt1 TG group were lower than WT group, which was significantly increased after MP, while the expression of Claudin-2 exhibited the opposite effect.

Conclusions

Keratin 1 maintains the intestinal barrier by upregulating TJ proteins in UC.

中文翻译：

---

角蛋白 1 在溃疡性结肠炎中维持肠道屏障

背景

肠道机械屏障在溃疡性结肠炎（UC）的发病机制中起关键作用。我们之前的研究表明角蛋白 1 (KRT1) 在 UC 中下调，但 KRT1 影响肠道屏障的机制仍然未知。

目标

探讨KRT1在UC肠屏障中的作用机制。

方法

在黏膜愈合 (MH) 前后从 20 名 UC 患者和 15 名健康对照中收集结肠组织。通过 PCR、蛋白质印迹和免疫组织化学 (IHC) 测量 KRT1 的表达。在krt1转基因（TG）小鼠中建立葡聚糖硫酸钠（DSS）诱导的结肠炎模型，并用甲基强的松龙（MP）处理小鼠以探索KRT1在肠屏障中的作用。通过 DAI 评分、结肠、脾脏和 H&E 评估炎症。用相同方法分析小鼠中KRT1和紧密连接(TJ)蛋白的表达。

结果

MH后KRT1在UC中的转录和表达减少并恢复，但未达到健康对照的水平。与临床结果相似，krt1的表达在 DSS 诱导的结肠炎中降低，在 MP 后上调。此外，krt1 TG 组比野生型 (WT) 组表现出更少的炎症。DSS诱导后Occludin和ZO-1的表达下降，krt1 TG组Occludin和ZO-1的下降低于WT组，MP后明显增加，而Claudin-2的表达则相反.

结论

角蛋白 1 通过上调 UC 中的 TJ 蛋白来维持肠道屏障。