肠道Foxl1+细胞衍生CXCL12通过调节细胞代谢来维持上皮质平衡
Mayu Yagita-Sakamaki1,2, Takayoshi Ito1, Taiki Sakaguchi1
1Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
International immunology
|January 8, 2025
概括
介质细胞分泌CXCL12,它调节肠道上皮细胞的新陈代谢. 这一过程通过调节美酸盐-胆固醇通路来抑制ApcMin/+小鼠的瘤进展.
科学领域:
- 胃肠病学 胃肠病学
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 介质细胞调节肠道干细胞 (ISC),但非ISC利基因素的作用尚不清楚.
- 主体和微生物代谢物影响子上皮层介质细胞.
研究的目的:
- 调查介质细胞衍生信号媒介如何影响表皮细胞平衡.
- 确定CXCL12在肠上皮细胞循环停止和瘤抑制中的作用.
主要方法:
- 分析了对PDGFRα高Foxl1高介质细胞的代谢物影响.
- 使用Foxl1-cre;Cxcl12f/f小鼠来评估CXCL12的功能.
- 研究了美酸盐-胆固醇合成途径和上皮细胞中的AMPK/SREBP信号传递.
- 在Cxcl12缺乏的ApcMin/+小鼠中评估瘤的发展.
主要成果:
- 氨酸和GABA等代谢物调节介质细胞转录.
- 来自Foxl1高介质细胞的CXCL12通过美酸盐-胆固醇通路诱导上皮细胞循环停止.
- 由CXCL12诱导的AMPK酸化抑制了SREBP的成熟,抑制了美瓦酸路径的激活.
- 在介质细胞中Cxcl12缺乏促进ApcMin/+小鼠的瘤发育.
结论:
- 由Foxl1高介质细胞分泌的CXCL12对于肠道上皮质平衡至关重要.
- CXCL12操纵上皮细胞代谢,与ApcMin/+小鼠的瘤进展预防有关.
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