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

doi:10.3969/j.issn.1002-1949.2018.05.010

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.Conelusion Activation of Hippo signaling could promote capability of anti-oxidative stress of mMSCs via modulation of Bcl-2/Baxin vitro.