氨酸-NFATc通路调节BAL液体细胞外囊中的脂质介质,从而调节微血管内皮细胞屏障功能
Manjula Karpurapu1, Yunjuan Nie2, Sangwoon Chung1
1Division of Pulmonary, Critical Care and Sleep Medicine, Ohio State University Wexner Medical Center, Davis Heart and Lung Research Institute, Columbus, OH, United States.
脂聚糖 (LPS) 触发细胞外囊泡 (EV),携带甲基酸 (AA) 代谢物,使急性肺损伤 (ALI) 恶化. 抑制氨酸-NFATc通路可以减少这些有害的EV,并减轻ALI.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 生物化学 生化学
背景情况:
- 细胞外囊泡 (EVs) 是细胞间通信的关键媒介.
- 激活的T细胞细胞质成员3 (NFATc3) 途径的核因子被脂聚糖 (LPS) 激活,并在急性肺损伤 (ALI) 中发挥作用.
- 氨酸-NFATc通路在调节EV脂质含量的作用及其对ALI病原性的贡献尚不清楚.
研究的目的:
- 调查氨酸-NFATc通路是否调节了EVs的脂质含量.
- 为了确定这些脂质修饰的EV是否有助于ALI.
- 探索抑制ALI中这种途径的治疗潜力.
主要方法:
- 使用液体染色体质谱法 (LC-MS/MS) 来分析来自支气管支气管洗液 (BALF) 的EV脂质介质.
- 在肺组织中测量细胞质酸酶A2 (cPLA2) 活性和相关酶 (COX2,LOXs) 的表达.
- 与小鼠肺微血管内皮细胞 (PMVEC) 和巨细胞进行共同培养实验,以评估EV诱导的屏障透性和细胞反应.
主要成果:
- 接受LPS治疗的小鼠的EV显示了阿拉基酸 (AA) 代谢物水平的显著增加,这些代谢物被氨酸抑制剂CNI103.3降低.
- ALI与cPLA2活性和cPLA2,COX2和脂氧酶的表达增加有关,所有这些都被CNI103.3抑制.
- 来自LPS治疗小鼠的EV增加了PMVEC单层的透性,而来自CNI103治疗小鼠的EV没有.
结论:
- 来自LPS治疗小鼠的BALF EVs携带NFATc依赖的AA衍生的脂质.
- 这些携带脂质的EV通过影响内皮屏障功能,有助于ALI的发病.
- 抑制氨酸-NFATc通路减少了EVs中的亲炎性脂质介质,并减轻了ALI.
更多相关视频
09:36Generation of an Immortalized Murine Brain Microvascular Endothelial Cell Line as an In Vitro Blood Brain Barrier Model
Published on: August 29, 2012
10:50Visualizing Impairment of the Endothelial and Glial Barriers of the Neurovascular Unit during Experimental Autoimmune Encephalomyelitis In Vivo
Published on: March 26, 2019
相关概念视频
Non-Canonical Wnt Signaling Pathways
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
Regulation of Angiogenesis and Blood Supply
Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Lipid-derived Compounds in the Human Body
Fat-soluble Vitamins
Fat-soluble vitamins, including vitamins A, D, E, and K, are required in minimal quantities, but their deficiencies can lead to severely abnormal physiological conditions. For example, vitamin A deficiency can cause night blindness, dry skin,...
