通过聚氨酸调节的RNA结合蛋白HuR稳定Cx43mRNA,增强肠上皮质屏障功能
Shelley R Wang1, Caroline G Mallard1, Cassandra A Cairns1
1Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, United States.
概括
多氨酸通过HuR蛋白稳定连xin 43 (Cx43) mRNA,增强肠道屏障功能. 这种机制对于在关键条件下维持肠道健康至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
背景情况:
- 肠道屏障功能障碍在严重疾病中很常见,导致细菌转移.
- 连素43 (Cx43) 对于细胞间通信和营养扩散至关重要.
- 多胺和RNA结合蛋白HuR是已知的细胞过程调节剂,但它们在Cx43调节中的作用尚不清楚.
研究的目的:
- 阐明聚氨酸调节肠上皮细胞 (IEC) 中Cx43表达的机制.
- 调查HuR在调解多胺和Cx43mRNA之间的相互作用中的作用.
- 确定这种调节通路对肠上皮质屏障功能的影响.
主要方法:
- 在IEC中使用RNA结合试验研究了HuR与Cx43mRNA的结合.
- 操纵了细胞聚胺水平,并评估了Cx43 mRNA稳定性和蛋白质水平.
- 利用宫外过度表达HuR和Cx43来拯救屏障功能缺陷.
- 研究了检查点激酶2过度表达在多胺缺乏细胞中的作用.
主要成果:
- HuR直接与Cx43mRNA的3'-未翻译区域结合,使其稳定并增加IEC中的Cx43表达.
- 多氨酸对HuR/Cx43mRNA复合物至关重要;耗尽会破坏Cx43mRNA的稳定,并降低Cx43蛋白质水平.
- 宫外HuR过度表达可以防止由聚胺枯竭引起的Cx43下降和屏障功能障碍.
- 过度表达Cx43可以逆转聚胺枯竭引起的屏障功能障碍;检查点激酶2可以增强HuR/Cx43相互作用和屏障功能.
结论:
- Cx43 mRNA是肠道上皮细胞中HuR的一个新目标.
- 多氨酸通过通过HuR调节Cx43mRNA稳定性来调节肠上皮质屏障功能.
- 这一途径突出了维护肠道屏障完整性的关键机制.
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