Molecular Framework of Mouse Endothelial Cell Dysfunction during Inflammation: A Proteomics Approach.
Molecular Framework of Mouse Endothelial Cell Dysfunction during Inflammation: A Proteomics Approach.
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DOI：
10.3390/ijms23158399
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发表时间：
2022-07-29
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
在脓毒症中观察到的细胞因子诱导的变化的一个关键方面是内皮细胞(ECs)的异常激活，启动了一系列炎症信号，导致白细胞黏附/迁移和器官损伤。由于对器官特异性EC的异质性及其对炎症反应的担忧，ECs的治疗靶向受到了阻碍。利用体外和电子计算机分析，我们全面分析了小鼠肺、肝和肾内皮细胞在暴露于临床相关的促炎细胞因子鸡尾酒后的蛋白质组学变化。将小鼠肺、肝、肾内皮细胞与肿瘤坏死因子-α/白介素1-β/干扰素-γ共同孵育4或24 h，模拟细胞因子诱导的变化。在内皮细胞上进行的无标记定量全球蛋白质组学和生物信息学分析为内皮细胞对炎症刺激随时间的变化和器官特异性差异的反应提供了一个分子框架。基因本体论和黑豹分析表明了为什么一些器官在早期更容易受到炎症的影响，并表明，随着炎症的进展，一些蛋白质的表达模式变得更加统一，同时表达额外的器官特有蛋白质。这些发现有助于深入了解EC对炎症反应的分子变化，并可支持针对不同器官内ECs的药物开发。数据可通过ProteomeXchange(识别符PXD031804)获得。
A key aspect of cytokine-induced changes as observed in sepsis is the dysregulated activation of endothelial cells (ECs), initiating a cascade of inflammatory signaling leading to leukocyte adhesion/migration and organ damage. The therapeutic targeting of ECs has been hampered by concerns regarding organ-specific EC heterogeneity and their response to inflammation. Using in vitro and in silico analysis, we present a comprehensive analysis of the proteomic changes in mouse lung, liver and kidney ECs following exposure to a clinically relevant cocktail of proinflammatory cytokines. Mouse lung, liver and kidney ECs were incubated with TNF-α/IL-1β/IFN-γ for 4 or 24 h to model the cytokine-induced changes. Quantitative label-free global proteomics and bioinformatic analysis performed on the ECs provide a molecular framework for the EC response to inflammatory stimuli over time and organ-specific differences. Gene Ontology and PANTHER analysis suggest why some organs are more susceptible to inflammation early on, and show that, as inflammation progresses, some protein expression patterns become more uniform while additional organ-specific proteins are expressed. These findings provide an in-depth understanding of the molecular changes involved in the EC response to inflammation and can support the development of drugs targeting ECs within different organs. Data are available via ProteomeXchange (identifier PXD031804).
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DOI：
10.1530/vb-22-0003
发表时间：
2022-02-01
期刊：
Vascular biology (Bristol, England)
影响因子：
--
作者：
Langston, Jordan C;Rossi, Michael T;Yang, Qingliang;Ohley, William;Perez, Edwin;Kilpatrick, Laurie E;Prabhakarpandian, Balabhaskar;Kiani, Mohammad F
通讯作者：
Kiani, Mohammad F
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
6.7
作者：
Jeong JH;Ojha U;Lee YM
通讯作者：
Lee YM
影响因子：
5.4
作者：
Aird, William C.
通讯作者：
Aird, William C.