模仿脏流量剪切有效诱导LECT2的聚合,LECT2是一种参与粉样性病的蛋白质
Jeung-Hoi Ha1, Yikang Xu2, Harsimranjit Sekhon1
1Department of Biochemistry and Molecular Biology, State University of New York Upstate Medical University, Syracuse, New York, USA.
The Journal of biological chemistry
|March 27, 2024
概括
微流体装置中的流体流量剪切,模仿脏血液流动,加速白细胞细胞衍生的化学毒素2 (LECT2) 氨基代. 这一过程被I40V突变进一步增强,为系统性粉样化症提供了洞察力.
科学领域:
- 生物物理学的生物物理.
- 腎臟病學 (nephrology) 是一種醫學專業.
- 生物化学 生物化学
背景情况:
- 包括ALECT2在内的全身性氨基粉症是由白细胞细胞衍生的化学毒素2 (LECT2) 聚合引起的.
- 众所周知,LECT2纤维生成是由损失和机械激动 (如震动) 加速的.
- 目前的模型不能完全代表体内条件,需要研究生理机械应激.
研究的目的:
- 研究由流体流动产生的生理剪切应力在驱动LECT2纤维化发生中的作用.
- 开发和利用一个微流体装置,模仿脏血流条件.
- 为了检查I40V突变在剪切应力下对LECT2聚合的影响.
主要方法:
- 开发一种具有逐渐缩小的微流体装置,分支道 (5毫米至20微米),以模拟脏微血管.
- 在微流体装置内对LECT2溶液应用生理剪切水平.
- 使用电子显微镜 (EM) 分析纤维的超结构,评估聚合动力学.
主要成果:
- 在生理剪切应激水平下,LECT2聚合和纤维细胞形成在24小时内被诱导.
- 微流体装置中的切削应力产生了与震动产生的纤维超结构不同的纤维超结构.
- I40V突变显著加速了LECT2纤维素的形成,增加了总体大小和密度.
结论:
- 生理剪切应激,特别是在类似脏的微流体通道中,是LECT2氨基基基因生成的强有力的驱动因素.
- I40V突变在剪切应力下加剧了LECT2聚合,突出了它在ALECT2病变发生中的作用.
- 微流体装置为研究血流如何影响蛋白质错折和氨基粉症提供了宝贵的平台.
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