通过TGF-β信号传导控制气道基底干细胞介导的肺修复
Tingting Zou1,2, Shiyu Zhang1,2, Mingzhe Liu1,2
1Institute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Science advances
|January 7, 2026
概括
改变呼吸道基底干细胞 (BCs) 中的增长因子β (TGF-β) 信号传递对于受伤后的肺部修复至关重要. 工程BC释放骨形态遗传蛋白7 (BMP7) 为肺纤维化提供了一种新的细胞治疗方法.
科学领域:
- 肺部医学 肺部医学
- 干细胞生物学 干细胞生物学
- 再生医学是一种再生医学.
背景情况:
- 呼吸道基底干细胞 (BCs) 对于受伤后的肺上皮质修复至关重要.
- 肺微环境在修复过程中影响BC功能的机制尚未完全理解.
研究的目的:
- 研究转化生长因子-β (TGF-β) 信号在BC介导的肺修复中的作用.
- 开发一种新的基于细胞的肺纤维化治疗策略.
主要方法:
- 利用蛋白质溶解向化马体 (PROTAC) 在人类BC细胞中降解Smad2/3.
- 在小鼠BC中进行TGF-β受体或Smad4的基因切除.
- 工程人类BCs释放骨形态遗传蛋白7 (BMP7) 作为对TGF-β的反应.
主要成果:
- TGF-β信号传递对于BC分化,迁移和屏障功能至关重要.
- 破坏BCs中TGF-β信号的破坏会损害肺部的修复,并促进增生.
- 在一个临床前模型中,工程BCs (iBMP7-BC) 增强了肺部修复和减少了纤维化.
结论:
- 在肺修复过程中,TGF-β信号极为关键地调节了气道基本干细胞的行为.
- 响应微环境的工程BCs代表了肺纤维化治疗肺纤维化的有前途的细胞治疗策略.
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