由帕尼斯细胞产生的诺图姆减弱了老化的肠表皮的再生
Nalle Pentinmikko1, Sharif Iqbal1, Miyeko Mana2
1Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland.
Nature
|July 12, 2019
概括
由于肠道中的Wnt信号衰退,老化的干细胞失去再生功能. 抑制已老的Paneth细胞产生的Wnt抑制剂Notum,恢复干细胞功能并促进组织再生.
科学领域:
- 老龄化研究
- 干细胞生物学
- 胃肠病学
背景情况:
- 在衰老过程中,干细胞功能下降会损害组织再生.
- 干细胞在衰老中的作用尚不清楚.
- 肠道干细胞是由帕内斯细胞调节的.
研究的目的:
- 研究衰老的肠表皮的再生潜力.
- 阐明与年龄相关的肠干细胞功能下降背后的机制.
- 确定向干细胞位是否可以恢复再生能力.
主要方法:
- 年轻人和老鼠肠表皮的再生潜力的比较.
- 研究了Wnt信号通路和Notum在老化的Paneth细胞中的作用.
- 在有机体模型中利用Notum和Wnt补充的基因向.
- 在小鼠中进行药理性Notum抑制以评估再生能力.
主要成果:
- 由于干细胞和位缺陷,肠上皮的再生潜力随着年龄的增长而减少.
- 陈旧的Paneth细胞产生更多的Notum,抑制Wnt信号和干细胞.
- 在老化的Paneth细胞中,高的mTORC1活性抑制了PPAR-α,增加了Notum.
- 在小鼠中,基因或药理上的抑制恢复了老化器官的功能,并增强了干细胞的再生.
结论:
- 通过抑制通过Notum传递Wnt信号,老化的Paneth细胞有助于干细胞老化.
- 向Notum可以恢复老化肠道干细胞的再生能力.
- 药物抑制促进老年人和化疗后的组织再生.
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