在肠道上皮质再生中,对于miR-143/145的一个必不可少的介质细胞功能
Raghu R Chivukula1, Guanglu Shi2, Asha Acharya2
1Medical Scientist Training Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Cell
|May 27, 2014
概括
微RNAs miR-143/145对于肠道修复至关重要,在介质细胞中起作用,而不是直接抑制上皮瘤. 它们的缺失会通过影响光滑肌肉和肌纤维细胞来损害伤口愈合.
科学领域:
- 分子生物学分子生物学
- 胃肠病学 胃肠病学
- 在瘤学瘤学.
背景情况:
- 在结肠癌中,miR-143/145微RNA (miRNA) 集群经常被下调.
- 过度表达miR-143/145抑制瘤形成,这表明瘤抑制作用.
- 以前的研究表明,这些miRNA在上皮组织中具有细胞自主功能.
研究的目的:
- 研究miR-143/145集群在肠道生理学和疾病中的体内功能.
- 为了确定负责肠道中miR-143/145功能的细胞区.
- 阐明miR-143/145影响表皮再生和瘤发生的机制.
主要方法:
- 通过针对性删除miR-143/145miRNA集群的小鼠的生成.
- 在淘汰赛小鼠中,评估受伤后的肠发育和上皮再生.
- 对miRNA表达模式和不同肠道区内的基因调节的分析.
- 调查光滑肌肉和肌纤维细胞功能及其对上皮质修复的影响.
主要成果:
- 在缺乏miR-143/145的小鼠中,肠道发育正常.
- 在没有miR-143/145.5的情况下,损伤后的上皮再生显著受损.
- miR-143/145的表达和功能仅在介质细胞区 (平滑肌肉和肌纤维细胞) 中.
- 由于光滑肌肉和肌纤维细胞功能障碍造成的再生障碍,与目标基因Igfbp5的抑制和改变的IGF信号传递有关.
结论:
- miR-143/145对于肠道上皮质伤口愈合至关重要,通过介质细胞起作用.
- 这些发现挑战了miR-143/145作为结肠癌中细胞自主上皮质瘤抑制剂的既定观点.
- 这项研究强调了介质细胞与上皮细胞相互作用在调节肠道修复中的关键作用.
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