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.

中文翻译：

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Moesin 是脓毒症内皮损伤的新型生物标志物

客观的。血管通透性增加和炎症是脓毒症的主要标志。Moesin (MSN) 是一种膜相关的细胞骨架蛋白，对血管内皮功能至关重要。本研究旨在评估MSN在脓毒症过程中在内皮损伤中的作用。方法。通过ELISA测量脓毒症患者的血清MSN。BALB/c 小鼠被注射不同剂量的脂多糖 (LPS) 或接受盲肠结扎和单或双穿刺 (CLP) 以模拟亚致死和致死脓毒症。治疗后，测量他们的血清 MSN 和 PCT 水平、湿肺重量（W/D 比）、支气管肺泡灌洗液（BALF）蛋白浓度和肺损伤评分。MSN 沉默对 LPS 改变的 Rock1/肌球蛋白轻链 (MLC)、NF- 的影响在体外测试了人类微血管内皮细胞 (HMEC) 中的κB和炎症因子，以及单层 HMEC 通透性。结果。与健康对照组相比，脓毒症患者血清 MSN 升高，并与脓毒症患者 SOFA 评分和血清 PCT 水平呈正相关。LPS注射液显着提高小鼠血清MSN和PCT表达、BALF蛋白水平和W/D比值，血清MSN水平与小鼠血清PCT、肺W/D比值和肺损伤评分呈正相关。以 CLP 建模的方式获得了类似的结果。LPS 增强 MSN、MLC、NF- κ在培养的 HMEC 中 B 磷酸化、Rock1 表达增加和炎症因子释放，而 MSN 沉默显着减轻了 LPS 诱导的 Rock1 和炎症因子表达、NF- κ B 和 MLC 磷酸化以及 HMEC 中的单层高渗透性。结论。增加的血清 MSN 通过激活 Rock1/MLC 和 NF-κB 信号传导导致脓毒症相关的内皮损伤，并且可能是评估脓毒症严重程度的潜在生物标志物。