NR5A2 的转录调节与胰腺的分化和炎症有关
Isidoro Cobo1, Paola Martinelli1, Marta Flández1
1Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre-CNIO, Madrid, Spain.
Nature
|February 15, 2018
概括
孤儿核受体NR5A2通常抑制胰腺炎症. 在小鼠和人类中减少NR5A2的表达会产生炎症前状态,促进胰腺癌的风险.
科学领域:
- 分子生物学
- 癌症学
- 胃肠病学
背景情况:
- 慢性炎症是各种癌症的一个已知的危险因素.
- 控制炎症和细胞分化的转录网络被认为是不同的.
- 孤儿核受体NR5A2参与多种代谢和发育过程.
研究的目的:
- 研究NR5A2在胰腺炎症和癌症中的作用.
- 探索胰腺中NR5A2,细胞分化和炎症基因网络之间的关系.
主要方法:
- 在异性Nr5a2缺陷 (Nr5a2+/-) 的小鼠中进行全球转录基因分析.
- 与显示NR5A2mRNA表达减少的人类胰腺组织进行比较.
- 研究了AP-1转录因子和Jun在观察到的表型中的作用.
主要成果:
- Nr5a2+/-小鼠在胰腺中表现出一种上皮细胞自主基础前炎症状态.
- 这种预炎症状态在人类胰腺中保持,NR5A2表达减少.
- NR5A2从分化转移到炎症基因,促进了依赖AP-1的转录.
- 在胰腺中删除Jun可以挽救炎症前的表型和缺陷的再生.
结论:
- 胰腺特异化转录网络也抑制炎症程序.
- 减少NR5A2表达可以颠覆这些网络,促进炎症并可能增加胰腺癌风险.
- 通过平衡分化和炎症,NR5A2在维持胰腺平衡中发挥着至关重要的作用.
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