人类多能干细胞衍生的皮肤有机体启用了Mycobacterium结核病菌感染的病理生理模型
Liang Yue1, Yating Liang1,2, Pengfei Zhong1,3
1Academy of Military Medical Sciences, Beijing, China.
Nature communications
|December 2, 2025
概括
皮肤器官有效地模拟了由Mycobacterium tuberculosis (Mtb) 引起的皮肤结核病 (CTB) 感染. 针对纤维细胞中的PI3K-AKT和AP1通路,可以减少Mtb诱导的皮肤纤维化.
科学领域:
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
- 皮肤病学 皮肤病学
背景情况:
- 皮肤结核病 (CTB) 涉及细胞外基质重塑和纤维化.
- 纤维细胞是纤维化中的关键,但它们在Mycobacterium结核病 (Mtb) 皮肤感染中的作用尚不清楚.
- 缺乏合适的体外模型阻碍了CTB研究.
研究的目的:
- 开发和利用人类皮肤有机体 (SKOs) 来建模CTB.
- 在SKO中调查MTB感染期间纤维细胞的作用和细胞变化.
- 确定驱动CTB纤维化的分子通路,并测试潜在的治疗方法.
主要方法:
- 人类诱导的多能干细胞干细胞衍生的SKO的生成.
- 用mtb感染SKO和随后的单细胞RNA测序.
- 药理上抑制PI3K-AKT和AP1信号通路.
主要成果:
- 感染mtb的SKO显示纤维细胞,原蛋白合成和降解 (MMP2,MMP14) 的增加.
- 在受感染的SKO中,神经细胞和脂肪细胞被破坏.
- 纤维化开始取决于纤维细胞PI3K-AKT和AP1的激活.
- 抑制PI3K-AKT和AP1可以减少纤维化和原沉积.
结论:
- SKOs可以作为研究CTB病原学的可行模型.
- 纤维细胞中的PI3K-AKT和AP1通路是Mtb诱导的皮肤纤维化的关键驱动因素.
- 针对这些途径为CTB相关纤维化提供了潜在的治疗策略.
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