肥胖通过IL-1β诱导的p38/MAPK信号通路调节造血干细胞命运决定
Jinxiao Yan1,2,3, Pan Zhang1,2,4, Xiru Liu1,2,3
1School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, China.
Stem cell research & therapy
|September 29, 2024
概括
肥胖引起的炎症激活了血液造血干细胞 (HSC) 中的p38/MAPK通路,促进了髓状细胞的分化. 阻止IL-1β扭转了这些变化,揭示了肥胖和HSC命运之间的直接联系.
科学领域:
- 免疫学 免疫学 免疫学
- 血液学 血液学 血液学
- 肥胖问题研究研究
背景情况:
- 肥胖会引发炎症,破坏免疫系统的平衡.
- 造血干细胞 (HSC) 对于免疫和血液细胞的产生至关重要.
- 肥胖驱动的炎症对HSC命运和骨髓利基的影响仍然不清楚.
研究的目的:
- 阐明肥胖促进炎症和HSC命运决定之间的关系.
- 调查炎症信号影响HSC造血功能的机制.
主要方法:
- 建立了一个高脂肪饮食 (HFD) 诱导肥胖的小鼠模型.
- 使用流细胞计和转录组测序分析HSC.
- 研究了IL-1β和p38/MAPK通路的作用,使用Anakinra进行抑制.
主要成果:
- HFD改变了骨髓的利基性质,减少了长期的HSC并促进了骨髓分化.
- 在肥胖小鼠中观察到高IL-1β和IL-1r1表达率,以及在HSC中激活的p38/MAPK信号传递.
- 抑制IL-1β使基因表达正常化,并逆转了HSC的命运.
结论:
- 肥胖引起的炎症通过高IL-1β的升高激活HSC中的p38/MAPK通路.
- 这种激活调节HSC分化,导致骨髓分化偏差.
- 肥胖,炎症和HSC骨髓分化偏差之间存在直接联系.
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