通过p53调节先天免疫反应和肠道微生物群
Amy Hui Ping Khor1, Tomoyuki Koguchi2, Hao Liu1
1Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Minato City, Tokyo, Japan.
Cancer science
|December 5, 2023
概括
瘤抑制剂p53调节先天免疫和肠道微生物群. 失去p53会增加对辐射毒性的敏感性,但抗生素可以提高生存率,突出p53的作用.
科学领域:
- 在瘤学瘤学.
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
背景情况:
- 瘤抑制剂p53在人类癌症中经常发生突变.
- p53调节了超出其规范性作用的多种细胞功能.
- 它在天生的免疫力和肠道微生物群中的作用是一个新兴的研究领域.
研究的目的:
- 研究p53在天生的免疫力中的作用及其对肠道微生物组合和辐射反应的影响.
- 确定参与先天免疫和肠道屏障功能的p53调节基因.
主要方法:
- 对被辐射的小鼠组织进行转录组分析.
- 基因本体学 (GO) 丰富分析.
- 16S rRNA测序用于分析肠道微生物组合.
- 评估辐射诱导的胃肠道 (GI) 毒性和p53-Knockout和野生型小鼠的生存率.
- 对抗生素给药对生存和胃肠道毒性的影响的评估.
- 在具有或没有p53突变的肝癌组织中分析Mbl2和Lcn2表达.
主要成果:
- p53显著诱导553个基因,天生的免疫力是一个高度相关的生物过程.
- 在辐射后的p53-Knockout小鼠中,Akkermansia的丰度下降.
- p53-Knockout小鼠对辐射诱导的胃肠道毒性的敏感性增加,生存率降低.
- 在p53-Knockout小鼠中,抗生素的使用显著改善了生存率,并防止了肠道毒性.
- 抗菌因子Mbl2和Lcn2由p53直接被交易活化并分泌到循环中.
- 在p53突变的肝癌中,MBL2和LCN2的表达减少.
结论:
- 通过先天性免疫点,p53在塑造肠道微生物群方面发挥着至关重要的作用.
- 通过p53调节抗菌因子 (Mbl2,Lcn2),有助于保护肠道屏障.
- 准肠道微生物组或p53调节的先天性免疫通路可能为治疗辐射毒性和癌症提供治疗策略.
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