FAK-p38信号传递是逆转矩阵刚度调节肝脏内皮细胞防御化的潜在目标
Xiaoyu Zhang1, Peiwen Li2, Jin Zhou2
1Center for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China; School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
Biomaterials
|January 3, 2024
概括
矩阵硬化通过细胞骨变化导致肝脏侧侧内皮细胞 (LSEC) 防御. 准焦粘附激酶 (FAK) 和p38-MK2通路可以恢复肝纤维化中的LSEC fenestrae.
科学领域:
- 细胞生物学 细胞生物学
- 机械生物学 机械生物学
- 肝脏病理生理学肝脏病理生理学
背景情况:
- 肝脏的鼻状内皮细胞 (LSEC) 对于肝脏的平衡至关重要.
- 肝纤维化涉及矩阵硬化,促进LSEC防御.
- 基础上LSEC防御的机械转导机制尚不清楚.
研究的目的:
- 调查矩阵刚度如何影响LSEC表型.
- 阐明参与LSEC防御的机械传导途径.
- 探索与LSEC功能相关的肝纤维化的潜在治疗点.
主要方法:
- 在硬度调节的水凝上培养的初级老鼠LSEC.
- 评估表型变化,包括细胞骨重组和 fenestrae 完整性.
- 关键信号通路组件的药理抑制 (FAK,p38-MK2).
主要成果:
- 增加的矩阵刚度通过细胞骨重组诱导LSEC防御.
- LSEC通过焦粘附激酶 (FAK) 检测到矩阵刚度,激活p38-MK2通路.
- 从纤维性肝脏的LSEC中抑制FAK或p38-MK2部分恢复的膜.
结论:
- 机械传导在肝纤维化期间显著影响LSEC防御.
- FAK-p38-MK2通路是硬度诱导的LSEC变化的关键调解者.
- 针对这种途径为肝纤维化提供了潜在的治疗策略.
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