Hyperoxia induces alveolar epithelial-to-mesenchymal cell transition

Area of Science:

• Pulmonary Medicine
• Cell Biology
• Pathology

Background:

• Myofibroblast accumulation is a hallmark of lung diseases requiring oxygen therapy.
• Epithelial-to-mesenchymal transition (EMT) of alveolar epithelial cells (AEC) is a potential source of these myofibroblasts.

Purpose of the Study:

• To investigate the effects of hyperoxia (high oxygen) on alveolar EMT.
• To elucidate the role of transforming growth factor-beta1 (TGF-β1) signaling in hyperoxia-induced alveolar EMT.

Main Methods:

• Used RLE-6TN cell lines and ex vivo lung slices to study hyperoxia effects.
• Analyzed protein and mRNA expression of epithelial and myofibroblast markers.
• Measured hydrogen peroxide (H2O2) levels and TGF-β1 activation.
• Utilized TGF-β1 inhibitors (SB-431542) in vitro and in vivo to assess their protective effects.

Main Results:

• Hyperoxia significantly decreased epithelial markers (pre-SpB, pro-SpC) and increased myofibroblast markers (α-SMA, vimentin) in lung cells and tissues.
• Hyperoxia increased H2O2 production, which activated TGF-β1 signaling and SMAD3 phosphorylation.
• Inhibition of TGF-β1 signaling prevented hyperoxia-induced α-SMA increase, E-cadherin downregulation, and attenuated alveolar histological changes.

Conclusions:

• Hyperoxia induces alveolar EMT, contributing to the pathology of lung diseases.
• The mechanism involves increased oxidative stress (H2O2) and subsequent activation of TGF-β1 signaling.
• Targeting TGF-β1 signaling may offer a therapeutic strategy to mitigate hyperoxia-induced lung damage.