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image of 2-DG Promotes the Proliferation, Differentiation, Migration, and Resistance to Oxidative Stress of Mesenchymal Stem Cells through Hippo Signaling

Abstract

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 HO 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. HO 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.

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2025-02-26
2025-03-15

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2-DG Promotes the Proliferation, Differentiation, Migration, and Resistance to Oxidative Stress of Mesenchymal Stem Cells through Hippo Signaling
Bentham Science Publishers ; https://doi.org/10.2174/0115665240327407250206112910
/content/journals/cmm/10.2174/0115665240327407250206112910
/content/journals/cmm/10.2174/0115665240327407250206112910
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  • Article Type:     Research Article
Keywords: migration ; proliferation ; differentiation ; Hippo signaling ; antioxidative stress ; Mesenchymal stem cells

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