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Activation of Wnt/β-catenin signalling promotes mesenchymal stem cells to repair injured alveolar epithelium induced by lipopolysaccharide in mice.

Cai SX, Liu AR, Chen S, He HL, Chen QH, Xu JY, Pan C, Yang Y, Guo FM, Huang YZ, Liu L, Qiu HB - Stem Cell Res Ther (2015)

Bottom Line: Lung tissue injury and repair assessment were examined using haematoxylin and eosin staining, lung injury scoring, Masson's trichrome staining and fibrosis scoring.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Critical Care Medicine, Zhong-da Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, People's Republic of China. cccsssxxx1980@163.com.

ABSTRACT

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Effect of control mouse mesenchymal stem cells (mMSCs) or mMSCs overexpressing β-catenin on acute lipopolysaccharide (LPS)-induced pulmonary inflammation. Levels of the proinflammatory cytokines (A) interleukin (IL)-1β, (B) IL-6 and anti-inflammatory cytokine (C) IL-10 in bronchoalveolar lavage fluid (BALF) in mice receiving MSCs at 3 days after LPS-induced acute respiratory distress syndrome were measured using enzyme-linked immunosorbent assay. Data are expressed as mean ± standard deviation (n = 6). *P < 0.05, versus normal saline (NS) + phosphate-buffered saline (PBS) group; #P < 0.05, versus LPS + PBS group; &P < 0.05, versus LPS+ mMSC control group.
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Fig6: Effect of control mouse mesenchymal stem cells (mMSCs) or mMSCs overexpressing β-catenin on acute lipopolysaccharide (LPS)-induced pulmonary inflammation. Levels of the proinflammatory cytokines (A) interleukin (IL)-1β, (B) IL-6 and anti-inflammatory cytokine (C) IL-10 in bronchoalveolar lavage fluid (BALF) in mice receiving MSCs at 3 days after LPS-induced acute respiratory distress syndrome were measured using enzyme-linked immunosorbent assay. Data are expressed as mean ± standard deviation (n = 6). *P < 0.05, versus normal saline (NS) + phosphate-buffered saline (PBS) group; #P < 0.05, versus LPS + PBS group; &P < 0.05, versus LPS+ mMSC control group.

Mentions: The levels of the pro-inflammatory cytokines IL-1β and IL-6 and the anti-inflammatory cytokine IL-10 were measured in the BALF of mice 3 days after LPS treatment using ELISA. All three cytokines were significantly higher in the LPS + PBS group than in the NS + PBS group (P < 0.05). IL-1β and IL-6 were reduced in the LPS + mMSC control and LPS + mMSC-Ctnnb1 groups compared with the LPS + PBS group (Figure 6A,B), while IL-10 was increased (Figure 6C) (P < 0.05). Comparatively, the decrease in IL-1β and increase in IL-10 observed in the LPS + mMSC-Ctnnb1 group were more significant than the changes observed in the LPS + mMSC control group (P < 0.05).Figure 6


Activation of Wnt/β-catenin signalling promotes mesenchymal stem cells to repair injured alveolar epithelium induced by lipopolysaccharide in mice.

Cai SX, Liu AR, Chen S, He HL, Chen QH, Xu JY, Pan C, Yang Y, Guo FM, Huang YZ, Liu L, Qiu HB - Stem Cell Res Ther (2015)

Effect of control mouse mesenchymal stem cells (mMSCs) or mMSCs overexpressing β-catenin on acute lipopolysaccharide (LPS)-induced pulmonary inflammation. Levels of the proinflammatory cytokines (A) interleukin (IL)-1β, (B) IL-6 and anti-inflammatory cytokine (C) IL-10 in bronchoalveolar lavage fluid (BALF) in mice receiving MSCs at 3 days after LPS-induced acute respiratory distress syndrome were measured using enzyme-linked immunosorbent assay. Data are expressed as mean ± standard deviation (n = 6). *P < 0.05, versus normal saline (NS) + phosphate-buffered saline (PBS) group; #P < 0.05, versus LPS + PBS group; &P < 0.05, versus LPS+ mMSC control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4414385&req=5

Fig6: Effect of control mouse mesenchymal stem cells (mMSCs) or mMSCs overexpressing β-catenin on acute lipopolysaccharide (LPS)-induced pulmonary inflammation. Levels of the proinflammatory cytokines (A) interleukin (IL)-1β, (B) IL-6 and anti-inflammatory cytokine (C) IL-10 in bronchoalveolar lavage fluid (BALF) in mice receiving MSCs at 3 days after LPS-induced acute respiratory distress syndrome were measured using enzyme-linked immunosorbent assay. Data are expressed as mean ± standard deviation (n = 6). *P < 0.05, versus normal saline (NS) + phosphate-buffered saline (PBS) group; #P < 0.05, versus LPS + PBS group; &P < 0.05, versus LPS+ mMSC control group.
Mentions: The levels of the pro-inflammatory cytokines IL-1β and IL-6 and the anti-inflammatory cytokine IL-10 were measured in the BALF of mice 3 days after LPS treatment using ELISA. All three cytokines were significantly higher in the LPS + PBS group than in the NS + PBS group (P < 0.05). IL-1β and IL-6 were reduced in the LPS + mMSC control and LPS + mMSC-Ctnnb1 groups compared with the LPS + PBS group (Figure 6A,B), while IL-10 was increased (Figure 6C) (P < 0.05). Comparatively, the decrease in IL-1β and increase in IL-10 observed in the LPS + mMSC-Ctnnb1 group were more significant than the changes observed in the LPS + mMSC control group (P < 0.05).Figure 6

Bottom Line: Lung tissue injury and repair assessment were examined using haematoxylin and eosin staining, lung injury scoring, Masson's trichrome staining and fibrosis scoring.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Critical Care Medicine, Zhong-da Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, People's Republic of China. cccsssxxx1980@163.com.

ABSTRACT

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus