Dataset Information

Mesenchymal stem cells with downregulated Hippo signaling attenuate lung injury in mice with lipopolysaccharide?induced acute respiratory distress syndrome.

ABSTRACT: Mesenchymal stem cell (MSC)?mediated repair of injured alveolar epithelial cells is a promising potential cure for acute respiratory distress syndrome (ARDS); however, the repairing effect of MSCs is limited by poor homing and differentiation. Our previous study revealed that the inhibition of the Hippo signaling pathway promotes the proliferation, migration and differentiation of MSCs in vitro, leading to the hypothesis that MSCs with downregulated Hippo signaling could further ameliorate lipopolysaccharide (LPS)?induced ARDS in vivo. In the current study, mouse bone marrow?derived MSCs (mMSCs) with downregulated Hippo signaling were constructed by shRNA?mediated knockdown of large tumor suppressor kinase 1 (Lats1) and were intratracheally administered to LPS?induced mouse models of ARDS. The inhibition of Hippo signaling increased the retention of mMSC in ARDS lung tissue and their differentiation toward alveolar type II epithelial cells. Furthermore, mMSCs with downregulated Hippo signaling led to a decreased lung wet weight/body weight ratio, decreased total protein and albumin concentrations in bronchoalveolar lavage fluid, decreased levels of proinflammatory factors and increased levels of anti?inflammatory factors. Finally, mMSCs with downregulated Hippo signaling improved pathological changes and decreased pulmonary fibrosis in lungs of mice with ARDS. These results suggest that the inhibition of the Hippo signaling pathway in mouse mMSCs by knockdown of Lats1 could further improve the protective effects of mMSCs against epithelial damage and the therapeutic potential of mMSCs on mice with ARDS.

SUBMITTER: Li L

PROVIDER: S-EPMC6365074 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mesenchymal stem cells with downregulated Hippo signaling attenuate lung injury in mice with lipopolysaccharide‑induced acute respiratory distress syndrome.

Li Lang L Dong Liang L Zhang Jiangqian J Gao Fei F Hui Jiaojie J Yan Jie J

International journal of molecular medicine 20181231 3

Mesenchymal stem cell (MSC)‑mediated repair of injured alveolar epithelial cells is a promising potential cure for acute respiratory distress syndrome (ARDS); however, the repairing effect of MSCs is limited by poor homing and differentiation. Our previous study revealed that the inhibition of the Hippo signaling pathway promotes the proliferation, migration and differentiation of MSCs in vitro, leading to the hypothesis that MSCs with downregulated Hippo signaling could further ameliorate lipop ...[more]

PMID: 30628652

Similar Datasets

Project description:BACKGROUND:Lung diseases such as acute respiratory distress syndrome (ARDS) have a high incidence worldwide. The current drug therapies for ARDS have supportive effects, making them inefficient. New methods such as stromal cell therapy are needed for this problem. METHODS:This research was performed with ten New Zealand rabbits in two groups. Bone marrow aspiration was performed on the treated group, and mesenchymal stem cells were isolated and cultured. The experimental model of ARDS was induced using LPS from Escherichia coli strain O55:B5. Then, 1010 bone marrow mesenchymal stem cells (BM-MSCs) were autologously transplanted intrapulmonary in the treatment group, and 1-2?ml of PBS in the control group. The clinical signs, computed tomographic (CT) scans, echocardiography, blood gas analysis, complete blood count, and cytokine levels were measured before and at 3, 6, 12, 24, 48, 72, and 168?h after BM-MSC transplant. Finally, the rabbits were killed, and histopathological examination was performed. RESULTS:The results showed that BM-MSCs decreased the severity of clinical symptoms, the number of white blood cells and heterophils in the blood, the total cell count, and number of heterophils and macrophages in bronchoalveolar lavage, and balanced the values of arterial blood gases (increase in partial pressure of oxygen and O2 saturation and decrease in the partial pressure of carbon dioxide). They also downregulated the tumor necrosis factor (TNF)-? and interleukin (IL)-6 concentrations and increased the IL-10 concentrations at different times compared with time 0 and in the control group, significantly. In the CT scan, a significant decrease in the Hounsfield units and total lung volume was found by echocardiography, and in comparing the two groups, a significant difference in the parameters was noticed. The histopathology demonstrated that the BM-MSCs were able to reduce the infiltration of inflammatory cells and pulmonary hemorrhage and edema. CONCLUSIONS:This study indicated that BM-MSCs play a significant role in the repair of lung injury.

Dataset Information

Mesenchymal stem cells with downregulated Hippo signaling attenuate lung injury in mice with lipopolysaccharide?induced acute respiratory distress syndrome.

Publications

Mesenchymal stem cells with downregulated Hippo signaling attenuate lung injury in mice with lipopolysaccharide‑induced acute respiratory distress syndrome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets