Activation of Wnt/β-catenin signalling promotes mesenchymal stem cells to repair injured alveolar epithelium induced by lipopolysaccharide in mice.
Activation of Wnt/β-catenin signalling promotes mesenchymal stem cells to repair injured alveolar epithelium induced by lipopolysaccharide in mice.
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Wnt/β-连环蛋白信号激活促进间充质干细胞修复脂多糖诱导的小鼠肺泡上皮损伤
DOI：
10.1186/s13287-015-0060-y
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发表时间：
2015-04-11
影响因子：
7.5
通讯作者：
Qiu HB
中科院分区：
文献类型：
--
作者：
Cai SX;Liu AR;Chen S;He HL;Chen QH;Xu JY;Pan C;Yang Y;Guo FM;Huang YZ;Liu L;Qiu HB
骨髓间充质干细胞（MSCs）在急性呼吸窘迫综合征（ARDS）中具有再上皮化和恢复的潜力。在先前的体外研究中，结果显示经典的Wnt/β-catenin通路促进MSC分化为II型肺泡上皮细胞，赋予对氧化应激的抵抗力，并促进其迁移，这表明Wnt/β-catenin通路可能是小鼠MSC在ARDS中的治疗作用的关键机制之一。将稳定转染β-catenin或绿色荧光蛋白对照的小鼠骨髓间充质干细胞移植到脂多糖诱导的ARDS小鼠体内。采用苏木精-伊红染色、肺损伤评分、Masson三色染色和纤维化评分等方法评价肺组织损伤和修复情况。通过使用NIR 815染料标记和追踪MSC、免疫荧光染色和Western免疫印迹分析来测定小鼠MSC的归巢和分化。采用酶联免疫吸附法检测支气管肺泡灌洗液中细胞因子和蛋白质含量，评价炎症和通透性。在这项研究中，β-连环蛋白过表达的MSC植入导致比GFP对照更显著的效果，包括MSC在肺中的保留，分化为II型肺泡上皮细胞，肺泡上皮通透性的改善和肺组织的病理损伤。结果提示，小鼠MSCs通过过表达β-catenin激活经典Wnt/β-catenin通路，可进一步增强小鼠MSCs对上皮细胞损伤的保护作用，提高小鼠MSCs对ARDS小鼠的治疗效果。
Mesenchymal stem cells (MSCs) have potential for re-epithelization and recovery in acute respiratory distress syndrome (ARDS). In a previous in vitro study, the results showed that the canonical Wnt/β-catenin pathway promoted the differentiation of MSCs into type II alveolar epithelial cells, conferred resistance to oxidative stress, and promoted their migration, suggesting that the Wnt/β-catenin pathway might be one of the key mechanisms underling the therapeutic effect of mouse MSCs in ARDS. Mouse MSCs stable transfected with β-catenin or green fluorescent protein control were transplanted intratracheally into the ARDS mice induced by lipopolysaccharide. Lung tissue injury and repair assessment were examined using haematoxylin and eosin staining, lung injury scoring, Masson’s trichrome staining and fibrosis scoring. Homing and differentiation of mouse MSCs were assayed by labelling and tracing MSCs using NIR815 dye, immunofluorescent staining, and Western immunoblot analysis. The inflammation and permeability were evaluated by detecting the cytokine and protein measurements in bronchoalveolar lavage fluid using enzyme-linked immunosorbent assay. In this study, β-catenin-overexpressing MSC engraftment led to more significant effects than the GFP controls, including the retention of the MSCs in the lung, differentiation into type II alveolar epithelial cells, improvement in alveolar epithelial permeability, and the pathologic impairment of the lung tissue. These results suggest that the activation of canonical Wnt/β-catenin pathway by mouse MSCs by overexpressing β-catenin could further improve the protection of mouse MSCs against epithelial impair and the therapeutic effects of mouse MSCs in ARDS mice.
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DOI：
10.1165/rcmb.2002-0056rc
发表时间：
2002-12-01
影响因子：
6.4
作者：
Grove, JE;Lutzko, C;Krause, DS
通讯作者：
Krause, DS
影响因子：
4.4
作者：
Gupta, Naveen;Su, Xiao;Matthay, Michael A.
通讯作者：
Matthay, Michael A.
影响因子：
3.9
作者：
Ma, Nan;Gai, Hui;Zhong, Hong
通讯作者：
Zhong, Hong
影响因子：
3.5
作者：
Chapel, A;Bertho, JM;Thierry, D
通讯作者：
Thierry, D
影响因子：
--
作者：
Kollar K;Cook MM;Atkinson K;Brooke G
通讯作者：
Brooke G