通过临时解决的激酶网络产生质疑内皮膜屏障调节
Ling Wei1, Selasi Dankwa1, Kamalakannan Vijayan1
1Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA.
Life science alliance
|March 11, 2024
概括
一种新的方法,TREKING,绘制了随着时间的推移控制内皮质屏障功能的酶网络. 它确定了特定的途径,如MAPKAPK2/MK2,在不同的炎症条件下对屏障完整性至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生化学
- 系统生物学 系统生物学
背景情况:
- 基因酶调节内皮膜屏障功能,但它们的动态作用和信号网络尚未完全理解.
- 内皮屏障的完整性对于组织平衡和预防炎症至关重要.
研究的目的:
- 开发一种新的方法,即临时RESolved KInase网络生成 (TREKING),用于重建时间解析的信号网络.
- 在不同的炎症刺激下识别激酶和调节内皮屏障完整性的途径.
主要方法:
- TREKING集成了一个28酶抑制器屏幕与机器学习和网络重建.
- 使用的脑内皮细胞用血栓激发,有或没有TNF预条件.
- 采用了临时的西方涂抹和遗传/药物干预 (lentivirus介导的淘汰,药物向).
主要成果:
- 特雷金预测了100多个酶参与内皮屏障调节,揭示了特定条件的途径.
- 通过MAPK激活的蛋白激酶2 (MAPKAPK2/MK2) 显示出动态的作用,早期削弱了屏障,但在仅含血栓的刺激下,晚期加强了屏障.
- 鉴定了一个MAP3K20/ZAK-MAPK14/p38α轴,在单独血素条件下控制晚期MAPKAPK2/MK2激活.
结论:
- TREKING是一种强大的工具,用于剖析生物过程中的动态激酶信号网络.
- 激酶网络在调节内皮膜屏障功能的过程中表现出复杂的,特定条件的时间动态.
- 了解这些网络为影响内皮壁垒的炎症性疾病的治疗策略提供了洞察力.
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