肝素硫酸盐调节肌纤维细胞的异质性,并在膜形态发生过程中调节利基恒温
Hua He1,2,3, Chong Ma4,5,6, Wei Wei7
1Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China. hua.he@scu.edu.cn.
纤维细胞肝素硫酸盐 (HS) 对于肺部发育至关重要,通过维持肌纤维细胞种群来支持膜形成. 失去了HS导致了简化的气泡,突出显示HS.
科学领域:
- 肺部的发育 肺部的发育
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 气膜形态发生对于产后呼吸和气体交换至关重要.
- 这个过程涉及多种细胞类型之间的复杂协调.
- 细胞外基因组件在肺部发育中的特定作用尚未完全理解.
研究的目的:
- 为了研究纤维细胞衍生的肝素硫酸糖氨基甘 (HS-GAG) 在膜形成中的作用.
- 阐明HS-GAG调节气泡的机制.
- 在肺部发育过程中识别由HS-GAG调节的细胞和分子通路.
主要方法:
- 在肺纤维细胞中使用Gli1-CreER小鼠对HS合成酶基因 (Ext1) 的基因切除.
- 对膜结构和肌纤维细胞群的分析.
- 对WNT和FGF/MAPK信号通路的评估.
- 细胞增殖和细胞亡的评估.
主要成果:
- 肺纤维细胞中Ext1的删除导致了扩大和简化膜结构.
- 由于HS-GAG的消去,导致PDGFRαhi αSMA+膜肌纤维细胞的丧失.
- HS-GAG对于肌纤维细胞的增殖和生存至关重要,部分通过FGF/MAPK信号传递.
- 强制激活MAPK/ERK信号,部分挽救了膜简化和AT2细胞增殖.
结论:
- 纤维细胞衍生的HS-GAG对于在肺部发育过程中维持气囊是必不可少的.
- HS-GAG调节肌纤维细胞异质性和功能,影响膜上皮细胞的增殖和分化.
- 通过调节生物物理和生物化学线索,HS-GAG协调了功能性气交单元的生成.
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