Evidence for Scgb1a1(+) cells in the generation of p63(+) cells in the damaged lung parenchyma

Am J Respir Cell Mol Biol. 2014 Mar;50(3):595-604. doi: 10.1165/rcmb.2013-0327OC.


Transformation-related protein 63-expressing (p63(+)) basal cells are confined to the trachea in the mouse lung. However, after influenza virus infection or bleomycin treatment, patches of p63(+) cells were observed in the damaged lung parenchyma. To address whether the newly induced p63(+) cells are derived from the p63(+) basal cells, we performed lineage tracing. In a keratin 5 promoter-driven CreER system, although preexisting p63(+) basal cells were labeled by enhanced green fluorescent protein (EGFP) after tamoxifen treatment, none or only a small fraction (∼ 15%) of the p63(+) patches was labeled by EGFP after bleomycin treatment or influenza virus infection, respectively. In contrast, > 60% of p63(+) patches contained EGFP(+) cells in Scgb1a1-CreER transgenic system where club cells are labeled. Many p63(+) cells were found in bronchiole-like lumen structures with columnar cells at the lumen side. The columnar cells were positive for club cell marker Cyp2f2 and could be traced to the newly induced p63(+) cells. These results suggest that most of the newly induced p63(+) cells in the damaged parenchyma are likely derived from club cells rather than from p63(+) basal cells and that newly induced p63(+) cells may be involved in the regeneration of bronchioles.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Bleomycin
  • Cell Lineage
  • Cell Proliferation*
  • Cytochrome P-450 Enzyme System / metabolism
  • Disease Models, Animal
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Epithelial Cells / virology
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Influenza A virus / pathogenicity
  • Keratin-15
  • Keratin-5 / genetics
  • Lung / metabolism*
  • Lung / pathology
  • Lung / physiopathology
  • Lung / virology
  • Lung Injury / chemically induced
  • Lung Injury / genetics
  • Lung Injury / metabolism*
  • Lung Injury / pathology
  • Lung Injury / physiopathology
  • Lung Injury / virology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Fluorescence
  • Phosphoproteins / metabolism*
  • Promoter Regions, Genetic
  • Regeneration*
  • Trans-Activators / metabolism*
  • Uteroglobin / genetics
  • Uteroglobin / metabolism*


  • Biomarkers
  • Keratin-15
  • Keratin-5
  • Krt15 protein, mouse
  • Phosphoproteins
  • Scgb1a1 protein, mouse
  • Trans-Activators
  • Trp63 protein, mouse
  • enhanced green fluorescent protein
  • Bleomycin
  • Green Fluorescent Proteins
  • Cytochrome P-450 Enzyme System
  • Uteroglobin
  • Cyp2f2 protein, mouse