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硫化氢通过实验性结肠炎中核糖体蛋白S20的巯基化作用维持肠道屏障修复功能。

Hydrogen sulfide preserves intestinal barrier repair function through sulfhydration of RPS20 in experimental colitis.

作者信息

He Xuan, Li Jichang, Huang Zhihao, Xue Baoshuai, Zhu Jing, You Meiyi, Liu Xiaoyun, Wang Xin, Liu Yucun, Chen Shanwen, Wang Pengyuan

机构信息

Department of Gastrointestinal Surgery, Peking University First Hospital, Beijing, China.

AstraZeneca Investment (China) Co., Ltd., Shanghai, China.

出版信息

Sci Rep. 2025 May 21;15(1):17673. doi: 10.1038/s41598-025-02268-5.

Abstract

Patients with ulcerative colitis (UC) have a significantly impaired intestinal barrier. Hydrogen Sulfide (HS) is a gaseous mediator that makes notable contributions in a variety of diseases, such as reducing inflammatory response in colitis. The experimental content includes the establishment of a mouse DSS-induced colitis mouse model, mouse colon epithelial organoids culture, H&E staining and mass spectrometry analysis. We recognized that exogenous HS donor-GYY4137 significantly alleviated the symptoms in UC mice models and maintained Minichromosome Maintenance Complex Component 2 (MCM2) expression. CBS knockdown reduced the expression of sulfhydrated Ribosomal protein S20 (RPS20-ssh) and MCM2 in the mouse colon. Cell experiments indicated that the expression of RPS20-ssh, rather than total expression of RPS20, is responsible.Our investigation indicated that CBS-HS axis increases the sulfhydration level of RPS20, leading to enhanced binding between RPS20 and MCM2 mRNA, thereby promoting intestinal epithelial proliferation. This may provide a novel therapeutic strategy for the clinical treatment of colitis.

摘要

溃疡性结肠炎(UC)患者的肠道屏障功能显著受损。硫化氢(HS)是一种气体介质,在多种疾病中发挥着重要作用,比如减轻结肠炎中的炎症反应。实验内容包括建立小鼠葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠模型、小鼠结肠上皮类器官培养、苏木精-伊红(H&E)染色及质谱分析。我们发现外源性HS供体-GYY4137可显著减轻UC小鼠模型的症状并维持微小染色体维持蛋白复合物组分2(MCM2)的表达。胱硫醚-β-合成酶(CBS)基因敲低降低了小鼠结肠中硫氢化核糖体蛋白S20(RPS20-ssh)和MCM2的表达。细胞实验表明,起作用的是RPS20-ssh的表达,而非RPS20的总表达。我们的研究表明,CBS-HS轴增加了RPS20的硫氢化水平,导致RPS20与MCM2 mRNA之间的结合增强,从而促进肠上皮增殖。这可能为结肠炎的临床治疗提供一种新的治疗策略。

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