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


ABSTRACT:

Background

Pericytes are vascular mural cells and are embedded in the basement membrane of the microvasculature. Recent studies suggest a role for pericytes in lipopolysaccharide (LPS)-induced microvascular dysfunction and mortality, but the mechanisms of pericyte loss in sepsis are largely unknown.

Methods

By using a cecal ligation and puncture (CLP)-induced murine model of sepsis, we observed that CLP led to lung and renal pericyte loss and reduced lung pericyte density and pericyte/endothelial cell (EC) coverage.

Results

Up-regulated Friend leukemia virus integration 1 (Fli-1) messenger ribonucleic acid (RNA) and protein levels were found in lung pericytes from CLP mice in vivo and in LPS-stimulated lung pericytes in vitro. Knockout of Fli-1 in Foxd1-derived pericytes prevented CLP-induced pericyte loss, vascular leak, and improved survival. Disrupted Fli-1 expression by small interfering RNA inhibited LPS-induced inflammatory cytokines and chemokines in cultured lung pericytes. Furthermore, CLP-induced pericyte pyroptosis was mitigated in pericyte Fli-1 knockout mice.

Conclusions

Our findings suggest that Fli-1 is a potential therapeutic target in sepsis.

SUBMITTER: Li P 

PROVIDER: S-EPMC6217724 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Li Pengfei P   Zhou Yue Y   Goodwin Andrew J AJ   Cook James A JA   Halushka Perry V PV   Zhang Xian K XK   Wilson Carole L CL   Schnapp Lynn M LM   Zingarelli Basilia B   Fan Hongkuan H  

The Journal of infectious diseases 20181101 12


<h4>Background</h4>Pericytes are vascular mural cells and are embedded in the basement membrane of the microvasculature. Recent studies suggest a role for pericytes in lipopolysaccharide (LPS)-induced microvascular dysfunction and mortality, but the mechanisms of pericyte loss in sepsis are largely unknown.<h4>Methods</h4>By using a cecal ligation and puncture (CLP)-induced murine model of sepsis, we observed that CLP led to lung and renal pericyte loss and reduced lung pericyte density and peri  ...[more]

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