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催产素调节肠道干细胞的自我更新和分化

Junfei Liu¹, Mengnan Guo², Mingze Geng²

¹Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China; Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China; Shandong Provincial Clinical Research Center for digestive disease, Jinan 250012, China.

Cellular signalling

|December 21, 2025

概括

催产素 (OXT) 信号通过增强干细胞自我更新,促进肠道上皮再生. 这一途径涉及前列腺素E2 (PGE2) 和Hippo途径,为治疗化疗诱导的肠道损伤提供了潜力.

科学领域:

胃肠病学胃肠病学
细胞生物学细胞生物学
分子医学是分子医学.

背景情况:

肠道平衡依赖于受调节的上皮细胞增殖和分化.
催产素 (OXT) 是一种新的胃肠道激素,涉及到肠道损伤.
在肠上皮细胞 (IECs) 中OXT的作用需要进一步阐明.

研究的目的:

研究IEC中的OXT/OXTR信号轴的功能意义.
阐明OXT影响肠道上皮质再生的分子机制.
评估OXT在减轻肠道损伤方面的治疗潜力.

主要方法:

使用小鼠小肠器官来研究OXT/OXTR信号.
在IEC中使用了OXTR的药理抑制和遗传淘汰 (KO).
研究了OXT介导的前列腺素E2 (PGE2) 生产和EP4受体激活.
评估了YAP激活和Hippo路径调制.

主要成果:

通过OXT/OXTR信号,增强了IEC的扩散和差异化.
缺少OXTR会影响干细胞自我更新,减少帕内斯细胞,并恶化5-FU诱导的粘膜炎.
OXT上调调节了COX-1/COX-2以刺激PGE2的产生,从而激活了EP4.
由OXT驱动的效应依赖于PGE2/EP4信号和通过Hippo通路调节的YAP激活.

结论:

通过PGE2/EP4/Hippo/YAP信号级联,OXT协调肠道上皮的再生.
OXT促进干细胞自我更新,对肠道屏障完整性至关重要.
对于化疗引起的肠损伤,OXT 是一种潜在的治疗剂.

关键词:

5 - - 甲酸是一种5甲.氧化素是一种氧化素.在PGE2的基础上,PGE2 扩散和差异化扩散和差异化哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈

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