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USP38通过稳定BIRC5来保护肠上皮细胞免受缺血/再损伤
Mandong Pan1, Xianwei Huang1, Xiaodong Huang1
1Emergency Department, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, P. R. China.
Gastroenterology report
|March 28, 2025
概括
骨髓中介细胞干细胞衍生的细胞外囊通过上调USP38.38.保护肠道缺血/再输 (II/R) 损伤,防止肠道缺血/再输 (II/R) 损伤. 这种机制涉及稳定BIRC5,从而提高肠上皮细胞的活力和减少损伤.
科学领域:
- 细胞生物学 细胞生物学
- 胃肠病学 胃肠病学
- 再生医学是一种再生医学.
背景情况:
- 肠道缺血/再输液 (II/R) 是一种严重的疾病,死亡率高,治疗策略有限.
- 骨髓介质干细胞衍生的细胞外囊泡 (BM-MSC-EVs) 在治疗II/R损伤方面表现有前途,但它们的潜在机制需要阐明.
- 无素-蛋白酶体系统,包括无素特异蛋白酶 (USP),在II/R中起作用,但具体的USP功能仍然不清楚.
研究的目的:
- 在细胞水平上研究BM-MSC-EVs在肠道缺血/再输液 (II/R) 损伤中的保护机制.
- 确定在II/R中泛素特异蛋白酶38 (USP38) 的作用及其与BIRC5.5的相互作用.
- 在II/R细胞模型中评估USP38过度表达BM-MSC-EVs的治疗潜力.
主要方法:
- 在IEC-6肠上皮细胞中使用氧气-葡萄糖剥夺/再输液 (OGD/R) 建立了肠道缺血/再输液 (II/R) 的体外模型.
- 使用定量PCR和西式涂抹来评估USP表达. 测量了细胞活力,细胞亡,迁移和活性氧物种 (ROS).
- 协同免疫沉 (Co-IP) 和西部抹迹被用来调查USP38和BIRC5之间的相互作用,并分析BIRC5的无处不在和稳定性.
主要成果:
- 在OGD/R治疗的肠上皮细胞中,USP38的表达显著降低.
- BM-MSC-EV治疗增加了USP38表达,改善了细胞活力,减少了细胞亡,增强了迁移,并降低了ROS水平.
- USP38通过减少其无处不在性来直接与BIRC5相互作用和稳定,而BIRC5的淘汰取消了USP38的保护作用.
结论:
- USP38在肠上皮细胞中起着保护作用,防止缺血/反 (I/R) 损伤.
- USP38增强了BIRC5的稳定性,从而减轻了I/R诱导的细胞损伤.
- USP38-过度表达的BM-MSC-EVs为II/R损伤提供了增强的治疗潜力.
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