Fli-1 Governs Pericyte Dysfunction in a Murine Model of Sepsis

Area of Science:

• Cell Biology
• Immunology
• Vascular Biology

Background:

• Pericytes are crucial mural cells within the microvasculature.
• Pericyte loss is implicated in sepsis-induced microvascular dysfunction and mortality.
• Mechanisms underlying pericyte loss during sepsis remain poorly understood.

Purpose of the Study:

• To investigate the role of Friend leukemia virus integration 1 (Fli-1) in sepsis-induced pericyte loss.
• To explore Fli-1 as a potential therapeutic target for sepsis.

Main Methods:

• Utilized a cecal ligation and puncture (CLP) murine model of sepsis.
• Assessed pericyte loss, vascular leak, and survival in wild-type and Fli-1 knockout mice.
• Examined Fli-1 expression in lung pericytes in vivo and in vitro following LPS stimulation.

Main Results:

• CLP induced significant pericyte loss in lungs and kidneys, reducing pericyte coverage.
• Upregulated Fli-1 mRNA and protein levels were observed in pericytes during sepsis.
• Fli-1 knockout in pericytes protected against CLP-induced pericyte loss, vascular leak, and improved survival.
• Inhibition of Fli-1 reduced inflammatory cytokine and chemokine production and mitigated pyroptosis.

Conclusions:

• Fli-1 plays a critical role in sepsis-induced pericyte loss and associated pathologies.
• Targeting Fli-1 presents a promising therapeutic strategy for sepsis management.