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Alveolar CCN1 is Associated with Mechanical Stretch and Acute Respiratory Distress Syndrome Severity.
American Journal of Physiology-Lung Cellular and Molecular Physiology ( IF 3.6 ) Pub Date : 2020-09-16 , DOI: 10.1152/ajplung.00073.2020
Eric D Morrell 1, 2 , Serge Grazioli 3 , Chi Hung 1 , Osamu Kajikawa 1 , Susanna Kosamo 1 , Renee D Stapleton 4 , Sina A Gharib 1 , Laura Amado-Rodríguez 5, 6 , Guillermo Albaiceta 5, 6 , Mark M Wurfel 1 , Gustavo Matute-Bello 1, 2
Affiliation  

The cellular communication network factor 1 (CCN1) is a matricellular protein that can modulate multiple tissue responses including inflammation and repair. We have previously shown that adenoviral overexpression of Ccn1 is sufficient to cause acute lung injury in mice. We hypothesized that CCN1 is present in the airspaces of lungs during the acute phase of lung injury and higher concentrations are associated with acute respiratory distress syndrome (ARDS) severity. We tested this hypothesis by measuring: 1) CCN1 in bronchoalveolar lavage fluid (BALF) and lung homogenates from mice subjected to ventilation-induced lung injury (VILI); 2) Ccn1 gene expression and protein levels in MLE-12 cells (alveolar epithelial cell line) subjected to mechanical stretch; 3) CCN1 in BALF from mechanically-ventilated humans with and without ARDS. BALF CCN1 concentrations and whole lung CCN1 protein levels were significantly increased in mice with VILI (n = 6) vs. non-injured controls (n = 6). Ccn1 gene expression and CCN1 protein levels were increased in MLE-12 cells cultured under stretch conditions. Subjects with ARDS (n = 77) had higher BALF CCN1 levels compared with mechanically-ventilated subjects without ARDS (n = 45) (p<0.05). In subjects with ARDS, BALF CCN1 concentrations were associated with higher total protein, sRAGE, and worse PaO2/FiO2 ratios (all p<0.05). CCN1 is present in the lungs of mice and humans during the acute inflammatory phase of lung injury and concentrations are higher in patients with increased markers of severity. Alveolar epithelial cells may be an important source of CCN1 under mechanical stretch conditions.

中文翻译:

肺泡 CCN1 与机械伸展和急性呼吸窘迫综合征的严重程度有关。

细胞通讯网络因子 1 (CCN1) 是一种基质细胞蛋白,可以调节多种组织反应,包括炎症和修复。我们之前已经表明 Ccn1 的腺病毒过表达足以导致小鼠急性肺损伤。我们假设 CCN1 在肺损伤的急性期存在于肺的气腔中,并且较高的浓度与急性呼吸窘迫综合征 (ARDS) 的严重程度有关。我们通过测量以下方法检验了这一假设:1) 支气管肺泡灌洗液 (BALF) 中的 CCN1 和来自遭受通气性肺损伤 (VILI) 的小鼠的肺匀浆;2) MLE-12细胞(肺泡上皮细胞系)机械拉伸后Ccn1基因表达及蛋白水平;3) BALF 中的 CCN1 来自有和没有 ARDS 的机械通气人。BALF CCN1 浓度和全肺 CCN1 蛋白水平在 VILI 小鼠(n = 6)与未受伤对照(n = 6)相比显着增加。在拉伸条件下培养的 MLE-12 细胞中,Ccn1 基因表达和 CCN1 蛋白水平增加。与没有 ARDS 的机械通气受试者(n = 45)相比,患有 ARDS 的受试者(n = 77)具有更高的 BALF CCN1 水平(p<0.05)。在 ARDS 受试者中,BALF CCN1 浓度与较高的总蛋白、sRAGE 和更差的 P 相关 与没有 ARDS 的机械通气受试者(n = 45)相比,患有 ARDS 的受试者(n = 77)具有更高的 BALF CCN1 水平(p<0.05)。在 ARDS 受试者中,BALF CCN1 浓度与较高的总蛋白、sRAGE 和更差的 P 相关 与没有 ARDS 的机械通气受试者(n = 45)相比,患有 ARDS 的受试者(n = 77)具有更高的 BALF CCN1 水平(p<0.05)。在 ARDS 受试者中,BALF CCN1 浓度与较高的总蛋白、sRAGE 和更差的 P 相关a O 2 /F i O 2比率(所有p<0.05)。在肺损伤的急性炎症阶段,CCN1 存在于小鼠和人类的肺中,并且在严重程度标志物增加的患者中浓度更高。在机械拉伸条件下,肺泡上皮细胞可能是 CCN1 的重要来源。
更新日期:2020-09-16
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