以太脂代谢的改变激活了保存的UPR-Xbp1-PDIA3/ERp60信号,以维持肠道平衡
Stephanie Makdissi1,2, Rihab Loudhaief1,2, Smitha George1,2
1Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
iScience
|March 4, 2025
概括
乙脂代谢对于维持肠道平衡至关重要. 它的破坏激活了未折叠的蛋白质反应,影响了原生细胞和上皮屏障功能,特别是在男性中.
科学领域:
- 胃肠病学 胃肠病学
- 细胞生物学 细胞生物学
- 代谢过程中的代谢.
背景情况:
- 肠上皮质平衡对于肠道健康至关重要,并且在结直肠癌和炎症性肠病等疾病中受到干扰.
- 虽然已知许多表皮再生的调节者,但代谢途径仍未得到充分研究.
- 代谢正在成为维护肠道上皮质平衡的关键,但被忽视的因素.
研究的目的:
- 为了研究以太脂质代谢在肠道上皮质平衡中的作用.
- 为了确定肠道原生细胞功能和上皮质屏障完整性的新型调节者.
- 阐明将代谢失调与肠道病理联系起来的信号通路.
主要方法:
- 利用 *Drosophila melanogaster* 作为一个模型生物来研究肠道平衡.
- 研究了乙脂代谢失调对肠道原始体的影响.
- 分析了未折叠蛋白反应 (UPR) 和下游信号通路的激活,包括Xbp1和PDIA3/ERp60.
- 研究了Jak/Stat信号在原生细胞增殖和上皮屏障功能中的作用.
主要成果:
- 乙脂代谢对于维持Drosophila*的肠上皮质平衡至关重要.
- 肠道原始体中乙醇脂的失调激活了未折叠的蛋白质反应 (UPR).
- UPR触发了Xbp1的激活和PDIA3/ERp60的上调,导致了Jak/Stat介导的原始细胞增殖.
- 这种信号级联损害了表皮屏障功能和生存,对男性有显著影响,但对女性没有.
结论:
- 乙醇脂和PDIA3/ERp60通路是肠道原生体恒常的关键调节者.
- 这种新陈代谢途径的改变可能导致肠道上皮的病态状况.
- Xbp1-ERp60-Jak/Stat轴代表了新陈代谢和肠道上皮质完整性之间的关键联系.
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