Molecular Framework of Mouse Endothelial Cell Dysfunction during Inflammation: A Proteomics Approach
| Autor: | Michael T. Rossi, Jordan C. Langston, Narender Singh, Carmen Merali, Qingliang Yang, Salim Merali, Balabhaskar Prabhakarpandian, Laurie E. Kilpatrick, Mohammad F. Kiani |
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| Rok vydání: | 2022 |
| Předmět: |
Inflammation
Proteomics Tumor Necrosis Factor-alpha Organic Chemistry Endothelial Cells General Medicine Catalysis Computer Science Applications Inorganic Chemistry Mice Animals Cytokines inflammation endothelium proteomics organ heterogeneity Endothelium Vascular Vascular Diseases Physical and Theoretical Chemistry Molecular Biology Spectroscopy |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 15; Pages: 8399 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms23158399 |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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