Molecular Framework of Mouse Endothelial Cell Dysfunction during Inflammation: A Proteomics Approach

Area of Science:

• Immunology
• Proteomics
• Cell Biology

Background:

• Sepsis involves dysregulated endothelial cell (EC) activation, driving inflammation and organ damage.
• Targeting ECs therapeutically is challenging due to organ-specific heterogeneity and inflammatory responses.

Purpose of the Study:

• To comprehensively analyze proteomic changes in mouse lung, liver, and kidney ECs exposed to proinflammatory cytokines.
• To understand the temporal and organ-specific molecular framework of EC response to inflammation.

Main Methods:

• In vitro incubation of mouse lung, liver, and kidney ECs with TNF-α/IL-1β/IFN-γ for 4 or 24 hours.
• Quantitative label-free global proteomics and bioinformatic analysis (Gene Ontology, PANTHER).

Main Results:

• Identified proteomic changes in ECs from different organs following cytokine exposure.
• Demonstrated organ-specific susceptibility to inflammation early on, with some protein patterns converging as inflammation progresses.
• Revealed expression of additional organ-specific proteins over time.

Conclusions:

• Provides a molecular framework for EC inflammatory responses, highlighting temporal and organ-specific differences.
• Informs the development of targeted therapies for ECs in various organs.
• Data available via ProteomeXchange (PXD031804).