Hypoxia promotes the skewed differentiation of umbilical cord mesenchymal stem cells toward type II alveolar epithelial cells by regulating microRNA-145

Mesenchymal stem cells (MSCs) are well recognized for their ability to differentiate into type II alveolar epithelial (ATII) cells in damaged lungs, which is critical for reepithelization and recovery in acute lung injury (ALI). However, the high level of transforming growth factor-β (TGF-β) commonly seen in injured lung tissues is also able to induce MSCs to differentiate into fibroblast-like cells. In this study, we found that hypoxia could promote umbilical cord mesenchymal stem cells (UCMSCs) differentiation into ATII cells rather than into fibroblast-like cells, and this effect was mainly mediated by microRNA-145 (miR-145), which could induce the inhibition of TGF-β signaling by targeting TGF-β receptor II (TGFβRII). Clarifying the function of hypoxia in the fate determination of MSCs is important for improving stem cell-based therapies for ALI. •Hypoxia promotes UCMSC-ATII differentiation and suppresses the tendency of UCMSCs to form fibroblast-like cells.•Hypoxia attenuates the TGF-β signaling in UCMSCs, leading to the inhibition of TGF-β-induced fibroblast differentiation.•Hypoxia positively regulates miR-145 expression which inhibits TGF-β signaling by targeting TGFβRII.