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在伤口关闭过程中EDA纤维素微架构和YAP转位
Jennifer Patten1, Patrick Halligan1, Ghazal Bashiri1
1Department of Bioengineering, Temple University, Philadelphia, Pennsylvania 19122, United States.
ACS biomaterials science & engineering
|March 3, 2025
概括
额外域A (EDA) 纤维蛋白 (Fn) 组织影响伤口愈合. 阻断EDAFn结合或YAP活动使纤维性伤口矩阵正常化,这表明促进再生修复的途径.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 组织工程是组织工程.
背景情况:
- 纤维蛋白 (Fn) 是一个关键的细胞外基质蛋白.
- 额外域A (EDA) Fn异型对组织修复至关重要,但与再生和纤维化有关.
- 细胞机械感知,特别是通过对相关蛋白 (YAP),影响伤口愈合结果.
研究的目的:
- 研究EDA Fn组织如何在正常和纤维性伤口关闭期间调节YAP转位.
- 探索EDA Fn矩阵组织在调解再生与纤维修复中的作用.
- 评估微环境硬度对EDA Fn组装和YAP活动的影响.
主要方法:
- 人体皮肤纤维细胞培养在软 (18 kPa) 和硬 (146 kPa) 聚二甲基酸基板上,模仿正常和纤维性伤口.
- 药理上抑制EDAFn结合 (Irigenin) 和YAP活动 (CA3).
- 分析EDA Fn矩阵组织 (纤维对齐和厚度) 和YAP转位.
主要成果:
- 较硬的基板导致EDA Fn矩阵与较薄的纤维对齐,表明张力增加.
- 阻止EDA Fn结合或YAP活动导致随机组织的,更厚的EDA Fn纤维,减少张力.
- 软基质上的纤维细胞显示YAP活动增加,而硬基质上的纤维细胞显示YAP活动减少.
- 在刚性基板上抑制EDAFn结合或YAP恢复了YAP活动的增加.
结论:
- EDA Fn 组织和 YAP 信号是相互连接的,并受到微环境硬度的影响.
- 在EDA Fn组织和YAP转位之间的信号中断可能会导致纤维性伤口关闭.
- 恢复正常的EDA Fn矩阵组织可能会将纤维修复转向再生.
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