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冷感应的FOXO1核运输有助于寒冷生存和组织存储
Xiaomei Zhang1,2,3, Lihao Ge4, Guanghui Jin1,2,5
1Department of Hepatic Surgery and Liver transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University, Guangzhou, China.
Nature communications
|April 3, 2024
概括
科学家们发现分叉箱O1 (FOXO1) 对于寒冷适应至关重要. 增强其核入口可以提高耐寒性,并延长器官的保存,为低温和移植提供新的治疗点.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生理学 生理学 生理学
背景情况:
- 感冒引起的伤害对低温疗法和器官保存构成重大挑战.
- 了解寒冷适应机制对于改进这些医疗干预措施至关重要.
研究的目的:
- 确定参与自主寒冷适应的关键分子因素.
- 阐明控制寒冷适应的监管网络.
- 探索提高耐寒性和器官保存的治疗目标.
主要方法:
- 在人体干细胞中调查了冷改变的染色质可访问性.
- 进行了集成的CUT&Tag/RNA-seq分析.
- 在人类细胞模型和斑马鱼幼虫中进行了寒冷生存实验.
- 在糖尿病前肥胖小鼠和器官保存中使用了Exportin-1抑制剂KPT-330.
主要成果:
- 确定了叉盒O1 (FOXO1) 作为适应寒冷的关键转录因子.
- 发现了一种对温度敏感的FOXO1核运输机制,涉及RANBP2,SUMO修饰的Importin-7和Exportin-1,以及FOXO1的SUMO相互作用动机.
- 证明,促进FOXO1核进入可以提高耐寒性,并显著延长人类和小鼠胰腺组织和小岛的保质期.
- 展示了14天冷藏的老鼠小岛的成功移植,恢复了糖尿病小鼠的正常血糖.
结论:
- FOXO1 是细胞寒冷适应的中央调节者.
- 新的FOXO1传输机制为调节寒冷耐受性提供了一个目标.
- 增强FOXO1核进入是改善低温疗法,器官保存和移植结果的有希望的治疗策略.
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