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

Gene. 2017 Sep 30:630:68-75. doi: 10.1016/j.gene.2017.08.006. Epub 2017 Aug 5.

Abstract

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.

Keywords: Hypoxia; MicroRNA-145; Transforming growth factor-β; Type II alveolar epithelial cells; Umbilical cord mesenchymal stem cells.

MeSH terms

  • Alveolar Epithelial Cells / cytology*
  • Alveolar Epithelial Cells / metabolism
  • Cell Differentiation*
  • Cell Hypoxia
  • Cell Line, Tumor
  • Cells, Cultured
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Oxygen / metabolism*
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / metabolism
  • Umbilical Cord / cytology

Substances

  • MIRN145 microRNA, human
  • MicroRNAs
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Oxygen