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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
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]