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| Effects of Hippo signaling on anti-oxidative stress of mesenchymal stem cells in vitro |
| Dong Liang, Li Lang, Hui Jiao-jie, Gao Fei, Wang Qiu-hui, Yang Lan, Zhang Jiang-qian, Yan Jie |
| Department of Critical Care Medicine, Wuxi People′s Hospital Affiliated to Nanjing Medical University, Wuxi 214023, China |
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Abstract Objective To explore the effects of Hippo signaling on anti-oxidative stress of marrow mesenchymal stem cells (mMSCs)in vitro. Methods mMSC sderived from bone marrow of C57BL/6 mice were identified using fluorescence-activated cell sorting analysis and the capabilities of osteogenic, chondrogenic and adipogenic differentiation were evaluated. The differentiation of mMSCs to alveolar epithelial type Ⅱ cells (AT Ⅱ)was induced by indirect co-culture with mouse lung epithelial cells(MLE-12)and small airway epithelial cell growth medium (SAGM). 2-deoxy-D-glucose (2-DG)and XMU-MP-1 were used to modulate the activation of Hippo signaling and the effect of Hippo signaling on the proliferation of mMSCs was evaluated using MTT assay. The scratch test and Transwell chamber test were used to analyze the effect of Hippo signaling on migration ability of mMSCs to conditioned medium of ARDS lung tissue. The role of Hippo signaling in the survival of mMSCs injured by H2O2 was evaluated using MTT assay, and the effect of Hippo signaling on anti-oxidative stress were analyzed through Bax and Bcl-2 using western blot. Results 2-DG could activate Hippo signaling in a dose-dependent manner while XMU-MP-1 could inhibit Hippo signaling. Oxidative stress was induced by H2O2 treatment. mMSCs death and inhibition of Hippo signaling induced by H2O2 were observed, those effects may associated with reduction of Bcl-2/Bax. Activation of Hippo signaling by 2-DG treatment could improve the survival of mMSCs through increase of Bcl-2/Bax, but those effects were reversed after inhibition of Hippo signaling by XMU-MP-1 treatment. Conclusion Activation of Hippo signaling could promote capability of anti-oxidative stress of mMSCs via modulation of Bcl-2/Baxin vitro.
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Corresponding Authors:
Li Lang, E-mail:shininglang@163.com
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| ［1］Restrepo MI, Chalmers JD, Song Y, et al. Year in review 2016: Respiratory infections, acute respiratory distress syndrome, pleural diseases, lung cancer and interventional pulmonology［J］.Respirology, 2017, 22(3):602-611.
［2］Horie S, Masterson C, Devaney J, et al. Stem cell therapy for acute respiratory distress syndrome: a promising future［J］. Curr Opin Crit Care, 2016, 22(1):14-20.
［3］Maron-Gutierrez T, Laffey JG, Pelosi P, et al. Cell-based therapies for the acute respiratory distress syndrome［J］. Curr Opin Crit Care, 2014, 20(1):122-131.
［4］Standiford TJ, Ward PA.Therapeutic targeting of acute lung injury and acute respiratory distress syndrome［J］.Transl Res, 2016, 167(1):183-191.
［5］Walter J, Ware LB, Matthay MA. Mesenchymal stem cells: mechanisms of potential therapeutic benefit in ARDS and sepsis［J］. Lancet Respir Med, 2014, 2(12):1016-1026.
［6］Gupta N, Krasnodembskaya A, Kapetanaki M, et al.Mesenchymal stem cells enhance survival and bacterial clearance in murine Escherichia coli pneumonia［J］.Thorax, 2012, 67(6):533-539.
［7］Khan MI, Czarnecka AM, Lewicki S, et al. Comparative gene expression profiling of primary and metastatic renal cell carcinoma stem cell-like cancer cells［J］. PLoS One, 2016, 11(11):e0165718.
［8］Tang Y, Weiss SJ.Snail/Slug-YAP/TAZ complexes cooperatively〖JP〗 regulate mesenchymal stem cell function and bone formation［J］.Cell Cycle, 2017, 16(5):399-405.
［9］Bellani G, Laffey JG, Pham T, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries［J］. JAMA, 2016, 315(8):788-800.〖ZK)〗
［10］Johnson CL, Soeder Y, Dahlke MH.Concise review: Mesenchymal stromal cell-based approaches for the treatment of acute respiratory distress and sepsis syndromes［J］.Stem Cells Transl Med, 2017, 6(4):1141-1151.
［11］Xiang B, Chen L, Wang X, et al.Transplantation of menstrual blood-derived mesenchymal stem cells promotes the repair of LPS-induced acute lung injury［J］.Int J Mol Sci, 2017, 18(4):E689.
［12］Hayes, Curley G, Ansari B, et al. Clinical review: Stem cell therapies for acute lung injury/acute respiratory distress syndrome-hope or hype［J］. Crit Care, 2012, 16(2):205.
［13］Johnson R, Halder G. The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment［J］. Nat Rev Drug Discov, 2014, 13(1):63-79.
［14］Zhang Q, Meng F, Chen S, et al. Hippo signalling governs cytosolic nucleic acid sensing through YAP/TAZ-mediated TBK1 blockade［J］. Nat Cell Biol, 2017, 19(4):362-374.
［15］Zhao B, Tumaneng K, Guan KL.The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal［J］.Nat Cell Biol, 2011, 13(8):877-883.
［16］Wang W, Xiao ZD, Li X, et al. AMPK modulates Hippo pathway activity to regulate energy homeostasis［J］. Nat Cell Biol, 2015, 17(4):490-499.
［17］Anand R, Maksimoska J, Pagano N, et al. Toward the development of a potent and selective organoruthenium mammalian sterile 20 kinase inhibitor［J］. J Med Chem, 2009, 52(6):1602-1611.
［18］Wang T, Liu YP, Wang T, et al. ROS feedback regulates the microRNA-19-targeted inhibition of the p47phox-mediated LPS-induced inflammatory response［J］. Biochem Biophys Res Commun, 2017, 489(4):361-368.
［19］Ware LB, Matthay MA. The acute respiratory distress syndrome［J］. N Engl J Med, 2000, 342(18):1334-1349.
［20］Li D, Xu Y, Gao CY, et al. Adaptive protection against damage of preconditioning human umbilical cord-derived mesenchymal stem cells with hydrogen peroxide［J］. Genet Mol Res, 2014, 13(3):7304-7317.
［21］Kim JY, Lee JS, Han YS, et al. Pretreatment with lycopene attenuates oxidative stress-Induced apoptosis in human mesenchymal stem cells［J］. Biomol Ther (Seoul), 2015, 23(6):517-524.
［22］Dubey PK, Masuda K, Nyati KK, et al. Arid5a-deficient mice are highly resistant to bleomycin-induced lung injury［J］. Int Immunol, 2017, 29(2):79-85.
［23］Mei SH, McCarter SD, Deng Y, et al.Prevention of LPS-induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1［J］.PLoS Med, 2007, 4(9):e269.
［24］Wang FW, Wang Z, Zhang YM, et al.Protective effect of melatonin on bone marrow mesenchymal stem cells against hydrogen peroxide-induced apoptosis in vitro［J］.J Cell Biochem, 2013, 114(10):2346-2355.
［25］王俊杰.骨髓间充质干细胞NMⅡ基因调控对吸入性损伤疗效及机制研究［D］.第二军医大学, 2016:1-87.
［26］刘慧莹.脐带间充质干细胞及气体治疗急性肺损伤的实验研究［D］.中国人民解放军军事医学科学院, 2014:1-128. |
| [1] |
Lu Yuan-zheng, Li Heng-jie, Wei Hong-yan, Yang Yan, Li Bo, Mao Hui, Yin Mei-xian, Hu Chun-lin, Liao xiao-xing. Sevoflurane inhalation attenuates the neuron apoptosis by modulation of Bcl-2/Bax expression after cardiac arrest in rats[J]. Chinese Journal of Critical Care Medicine, 2018, 38(4): 357-. |
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