原IV组装受细胞衍生基质中的流体流动的影响
Pinyuan Tian1, Nikki-Maria Koudis1, Mychel R P T Morais1
1Wellcome Centre for Cell-Matrix Research, School of Biological Science, Faculty of Biology, Medicine and Health, University of Manchester, UK.
Cells & development
|April 26, 2024
概括
基底膜组件受流体流动的影响. 层状流量重塑了IV原蛋白,而prolyl-4-hydroxylase (P4HA1) 倒置减少了IV原蛋白的分泌,特别是在流动下.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 细胞生物学 细胞生物学
- 生物材料科学 生物材料科学
背景情况:
- 脏过依赖于由细胞和内皮细胞组装的底层膜.
- 流体流对底层膜组装和组织的影响还不太清楚.
研究的目的:
- 为了研究层状流体的流动如何影响细胞衍生矩阵的组成和组装.
- 了解prolyl-4-hydroxylase (P4HA1) 在流媒体矩阵重塑中的作用.
主要方法:
- 在高流量生物反应器中共同培养细胞和质内皮细胞.
- 免疫光,矩阵图像分析和细胞衍生矩阵的蛋白质组分析.
- 在CRISPR-Cas9基因编辑中,用发光标记物 (HiBiT) 标记内源性COL4A2.
主要成果:
- 层状液体流动诱导了基底膜中的IV原体的重塑.
- 蛋白质组分析显示,在流动下,矩阵蛋白的丰度和组成发生了变化,包括P4HA1.1.
- 原IV分泌在静态和流动条件下是一致的,但P4HA1倒置显著减少了分泌,特别是在流动条件下.
结论:
- 流体流动显著影响细胞衍生基质的组成,修饰和组织.
- 这项研究提供了一种新的体外系统,用于研究发育和病的流动诱导矩阵改变.
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