持续激活P2X7受体是慢性炎症和肠道致癌变化的基础
Patricia Teixeira Santana1,2, Isadora Schmukler de Lima1, Karen Cristina da Silva E Souza1
1Department of Clinical Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, Brazil.
International journal of molecular sciences
|October 26, 2024
概括
通过腺三酸盐 (ATP) 和P2X7受体发出异常信号,导致IBD和CRC等肠道疾病的炎症和表观遗传变化. 准这种途径显示出对这些疾病的治疗前景.
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
背景情况:
- 与损伤相关的分子模式 (DAMPs) 的异常信号,例如细胞外腺三酸盐 (ATP),与各种健康障碍有关.
- 纯能受体P2X7作为免疫细胞中的关键危险传感器,调解细胞死亡和促炎细胞因子产生等功能.
- 持续的DAMP释放,包括ATP,可以导致表观遗传修饰,可能会影响炎症性肠病 (IBD) 和结直肠癌 (CRC) 等疾病的疾病表型.
研究的目的:
- 调查ATP-P2X7通路在肠道疾病的发病过程中的作用.
- 探索P2X7信号,表观遗传重编程和IBD和CRC的发展之间的联系.
- 评估针对肠道疾病中的ATP-P2X7途径的治疗潜力.
主要方法:
- 在IBD患者的肠道粘膜中分析P2X7表达.
- 在化学诱导的实验性结肠炎模型中评估P2X7阻塞效应.
- 研究P2X7在调节肠道微生物群组成中的作用.
- 检查下游信号通路,包括由P2X7激活和异生物微生物群触发的炎症体.
主要成果:
- 在IBD患者的肠道粘膜中,P2X7过度表达.
- P2X7阻塞表明对化学诱导的实验性结肠炎有保护作用.
- 有证据表明P2X7会影响肠道微生物群的组成.
- 不调节的P2X7信号,与微生物群信号相结合,促进炎症和结肠炎相关的CRC发展.
结论:
- ATP-P2X7通路在IBD和CRC背后的炎症过程中发挥着重要作用.
- 这种途径介导的表观遗传修饰有助于疾病病理学.
- 准ATP-P2X7轴为炎症性肠道疾病和相关癌症提供了一个有前途的治疗策略.
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