Evidence for pleural epithelial-mesenchymal transition in murine compensatory lung growth

PLoS One. 2017 May 19;12(5):e0177921. doi: 10.1371/journal.pone.0177921. eCollection 2017.


In many mammals, including rodents and humans, removal of one lung results in the compensatory growth of the remaining lung; however, the mechanism of compensatory lung growth is unknown. Here, we investigated the changes in morphology and phenotype of pleural cells after pneumonectomy. Between days 1 and 3 after pneumonectomy, cells expressing α-smooth muscle actin (SMA), a cytoplasmic marker of myofibroblasts, were significantly increased in the pleura compared to surgical controls (p < .01). Scanning electron microscopy of the pleural surface 3 days post-pneumonectomy demonstrated regions of the pleura with morphologic features consistent with epithelial-mesenchymal transition (EMT); namely, cells with disrupted intercellular junctions and an acquired mesenchymal (rounded and fusiform) morphotype. To detect the migration of the transitional pleural cells into the lung, a biotin tracer was used to label the pleural mesothelial cells at the time of surgery. By post-operative day 3, image cytometry of post-pneumonectomy subpleural alveoli demonstrated a 40-fold increase in biotin+ cells relative to pneumonectomy-plus-plombage controls (p < .01). Suggesting a similar origin in space and time, the distribution of cells expressing biotin, SMA, or vimentin demonstrated a strong spatial autocorrelation in the subpleural lung (p < .001). We conclude that post-pneumonectomy compensatory lung growth involves EMT with the migration of transitional mesothelial cells into subpleural alveoli.

MeSH terms

  • Animals
  • Epithelial-Mesenchymal Transition*
  • Lung / growth & development*
  • Lung / pathology*
  • Lung / surgery
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Organogenesis
  • Phenotype
  • Pleura / growth & development*
  • Pleura / pathology*
  • Pleura / surgery
  • Pneumonectomy*