title: Evidence for Scgb1a1(+) cells in the generation of p63(+) cells in the damaged lung parenchyma.
abstract: 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.
authors.affiliation: 1 Interdisciplinary Research Group in Infectious Diseases, Singapore-Massachusetts Institute of Technology Alliance for Research and Technology, Singapore; and.
authors.forename: Dahai
authors.initials: D
authors.lastname: Zheng
authors.forename: Lu
authors.initials: L
authors.lastname: Yin
authors.forename: Jianzhu
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001761:Bleomycin; D019070:Cell Lineage; D049109:Cell Proliferation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D009980:Influenza A virus / Q000472:pathogenicity; D053569:Keratin-15; D053555:Keratin-5 / Q000235:genetics; D008168:Lung / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D055370:Lung Injury / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D010750:Phosphoproteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012038:Regeneration; D015534:Trans-Activators / Q000378:metabolism*; D014598:Uteroglobin / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D053569:Keratin-15; D053555:Keratin-5; C492053:Krt15 protein, mouse; D010750:Phosphoproteins; C556390:Scgb1a1 protein, mouse; D015534:Trans-Activators; C486419:Trp63 protein, mouse; C485184:enhanced green fluorescent protein; D001761:Bleomycin; D049452:Green Fluorescent Proteins; D003577:Cytochrome P-450 Enzyme System; D014598:Uteroglobin; C110333:Cyp2f2 protein, mouse