Abstract
Objective Increased vascular permeability and inflammation are principal hallmark of sepsis. Moesin (MSN) is a membrane-associated cytoskeleton protein and crucial for the vascular endothelial function. This study is aimed at evaluating the role of MSN in endothelial injury during the process of sepsis. Methods Serum MSN in septic patients was measured by ELISA. BALB/c mice were injected with different doses of lipopolysaccharide (LPS) or underwent cecal ligation and single or double puncture (CLP) to mimic sublethal and lethal sepsis. After treatment, their serum MSN and PCT levels, wet to dry lung weights (W/D ratio), bronchoalveolar lavage fluid (BALF) protein concentrations, and lung injury scores were measured. The impact of MSN silencing on LPS-altered Rock1/myosin light chain (MLC), NF-κB, and inflammatory factors in human microvascular endothelial cells (HMECs), as well as monolayer HMEC permeability, was tested in vitro. Results Compared with healthy controls, serum MSN increased in septic patients and was positively correlated with SOFA scores and serum PCT levels in septic patients. LPS injection significantly increased serum the MSN and PCT expression, BALF protein levels, and W/D ratio, and the serum MSN levels were positively correlated with serum PCT, lung W/D ratio, and lung injury scores in mice. Similar results were obtained in the way of CLP modelling. LPS enhanced MSN, MLC, NF-κB phosphorylation, increased Rock1 expression, and inflammatory factors release in the cultured HMECs, while MSN silencing significantly mitigated the LPS-induced Rock1 and inflammatory factor expression, NF-κB, and MLC phosphorylation as well as the monolayer hyperpermeability in HMECs. Conclusions Increased serum MSN contributes to the sepsis-related endothelium damages by activating the Rock1/MLC and NF-κB signaling and may be a potential biomarker for evaluating the severity of sepsis.
Highlights
Sepsis is a leading cause of high morbidity and mortality worldwide, and it can lead to dysregulated host responses to infection, even acute multiple organ failure [1]
We found that the serum MSN levels in septic shock patients (1974:57 ± 838:15 pg/ml) were significantly higher than that in the sepsis group (1038:55 ± 477:19 pg/ml) and the healthy controls
Correlation analysis revealed that the levels of serum MSN in the septic patients were positively correlated with Sequential Organ Failure Assessment (SOFA) scores (r = 0:4918,p = 0:0008, Figure 1(b)) and serum PCT levels (r = 0:3455, p = 0:0232, Figure 1(c))
Summary
Sepsis is a leading cause of high morbidity and mortality worldwide, and it can lead to dysregulated host responses to infection, even acute multiple organ failure [1]. During the process of infection and sepsis, endothelial cells can initiate and propagate the inflammatory response, and systemic activation of the endothelium will disrupt the endothelium barrier [3, 4]. Such wide spreading vascular dysfunction leads to multiple organ failure and death. Identification of biomarkers for evaluating endothelial activation and injury will be of significance in early management of septic patients
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