VIPR1充当肠道神经检查点,抑制肠道干细胞驱动的上皮质再生,并加剧结肠炎
Chaoliang Li1, Haohao Wang1, Panrui Zhang2
1Department of Digestive Disease, The First Affiliated Hospital of USTC, State Key Laboratory of Immune Response and Immunotherapy, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China; Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
来自血管活性肠 (VIP) 神经元的神经信号通过VIP受体1 (VIPR1) 抑制肠干细胞 (ISC) 再生. 阻断VIPR1可以增强大肠炎期间的肠道修复,提供一种潜在的治疗策略.
科学领域:
- 胃肠病学 胃肠病学
- 神经科学是一个神经科学.
- 干细胞生物学 干细胞生物学
背景情况:
- 肠干细胞 (ISC) 对于上皮的更新至关重要.
- 神经调节在ISC行为中的作用,特别是在受伤期间,尚未完全理解.
研究的目的:
- 为了确定控制ISC再生能力的神经机制.
- 为了研究产生血管活性肠 (VIP) 的神经元在调节ISC活动中的功能.
主要方法:
- 在大肠炎的小鼠模型中研究了VIP-VIPR1信号轴.
- 在上皮细胞或ISC群体中利用了Vipr1的遗传删除.
- 检查了ERK-Notum-Wnt/β-catenin通路. 这是一个很好的例子.
主要成果:
- VIP-VIPR1信号作为神经元检查点,抑制ISC的增殖和再生.
- 在大肠炎期间,扩大的VIPergic神经元会放大这种通路,从而损害上皮质修复.
- 在ISC或上皮质中Vipr1的删除恢复了再生活动和缓解大肠炎.
- 在人类肠道模型中保留了VIP-VIPR1信号的抑制功能.
结论:
- VIPR1是一种ISC内在受体,介导神经抑制再生.
- 通过抑制ISC驱动的修复,VIP-VIPR1信号加剧了结肠炎期间的损伤.
- 向上皮质VIPR1阻塞可能会在诸如结肠炎之类的炎症性疾病中增强粘膜再生.
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