The Effects of Hypoxia on the Immune-Modulatory Properties of Bone Marrow-Derived Mesenchymal Stromal Cells

Figure 2

Molecular mechanisms involved in the proliferative and cytokine response of hypoxic BMSCs. Hypoxia-stabilized HIFs induce genes like APLN that, in return, activate the AKT/PKB pathway. This leads to inactivating phosphorylation of GSK3β releasing cyclin D1 from GSK3β-mediated inhibition. Data also suggest that the activation of the AKT/PKB results in the regulation of mTOR that affects both autophagic and translational activities of BMSCs. Besides mTOR, hypoxia also induces genes like EPRS and IEF4EBP1 that also contribute to the hypoxia-specific translational pattern, likely, to define composition of secreted immune-modulatory factors of BMSCs.