Background:Hippo signaling regulates the behavior and fate of
mesenchymal stem cells (MSCs), which are crucial for the repair and cure of acute
respiratory distress syndrome (ARDS). However, whether 2-deoxy-D-glucose (2-DG),
a specific activator of Hippo signaling, would further enhance the reparative effect of
MSCs in ARDS remains unclarified.Objective:This study aimed to determine whether 2-DG could promote the
proliferation, differentiation, migration, and resistance to oxidative stress of mouse
bone marrow-derived MSCs (mBMSCs).Methods:mBMSCs were isolated from C57BL/6 mice and differentiated into alveolar
type II epithelial (ATII) cells by noncontact coculture. The specific activator and
inhibitor 2-DG and 4-[(5,10-dimethyl-6-Oxo-6,10-dihydro-5h-pyrimido[5,4-B]thieno[3,2-
E][1,4]diazepin-2-Yl)amino]benzenesulfonamide (XMU-MP-1) were used to activate
and inhibit Hippo signaling, respectively. Oxidative stress-induced injuries were
induced by H2O2 treatment.Results:We observed that 2-DG activated Hippo signaling and promoted mBMSC
proliferation in a dose-dependent manner. 2-DG also promoted the differentiation of
mBMSCs into ATII cells and enhanced not only the horizontal and vertical migration of
mBMSCs but also mBMSC homing to injured lung tissue. H2O2 treatment inhibited
Hippo signaling and reduced the viability of mBMSCs by decreasing the Bcl-2/Bax
ratio, but 2-DG activated Hippo signaling and conferred mBMSCs with resistance to
oxidative stress by increasing the Bcl-2/Bax ratio. However, XMU-MP-1 suppressed
these effects to some extent.Conclusion:Through Hippo signaling, 2-DG promoted the proliferation, migration,
differentiation, and resistance to oxidative stress of mBMSCs, suggesting a novel
strategy for enhancing the reparative effects of MSCs in ARDS.