Ysasi, Alexandra B.Wagner, Willi L.Valenzuela, Cristian D.Kienzle, ArneServais, AndrewBennett, Robert D.Tsuda, AkiraAckermann, MaximilianMentzer, Steven2017-06-152017Ysasi, Alexandra B., Willi L. Wagner, Cristian D. Valenzuela, Arne Kienzle, Andrew B. Servais, Robert D. Bennett, Akira Tsuda, Maximilian Ackermann, and Steven J. Mentzer. 2017. “Evidence for pleural epithelial-mesenchymal transition in murine compensatory lung growth.” PLoS ONE 12 (5): e0177921. doi:10.1371/journal.pone.0177921. http://dx.doi.org/10.1371/journal.pone.0177921.http://nrs.harvard.edu/urn-3:HUL.InstRepos:33030017In 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.en-USMedicine and Health SciencesSurgical and Invasive Medical ProceduresRespiratory System ProceduresPneumonectomySurgical ExcisionPhysical SciencesChemistryChemical CompoundsOrganic CompoundsVitaminsB VitaminsBiotinOrganic ChemistryBiology and Life SciencesBiochemistryProteinsCytoskeletal ProteinsVimentinSpectrum Analysis TechniquesSpectrophotometryFluorimetryImage CytometryMicroscopyElectron MicroscopyScanning Electron MicroscopyThoracotomyChromatographic TechniquesPlanar ChromatographyThin-Layer ChromatographyImaging TechniquesFluorescence ImagingJournal Article2017-06-1510.1371/journal.pone.0177921