A cellular pathway involved in Clara cell to alveolar type II cell differentiation after severe lung injury

Regeneration of alveolar epithelia following severe pulmonary damage is critical for lung function. We and others have previously shown that Scgb1a1-expressing cells, most likely Clara cells, can give rise to newly generated alveolar type 2 cells (AT2s) in response to severe lung damage induced by e...

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Bibliographic Details
Published in:PloS one 2013-08, Vol.8 (8), p.e71028
Main Authors: Zheng, Dahai, Limmon, Gino V, Yin, Lu, Leung, Nicola H N, Yu, Hanry, Chow, Vincent T K, Chen, Jianzhu
Format: Article
Language:English
Subjects:
Alveolar Epithelial Cells - physiology
Alveoli
Animals
Biology
Bleomycin
Bronchioles - pathology
Bronchioles - physiopathology
Cell Differentiation
Cell morphology
Cytology
Differentiation (biology)
Embryogenesis
Embryonic development
Epithelial cells
Health aspects
Infections
Infectious diseases
Influenza
Influenza viruses
Interdisciplinary aspects
Intermediates
Lung diseases
Lung Injury - chemically induced
Lung Injury - pathology
Lung Injury - virology
Lungs
Medical research
Medicine
Mice
Mice, Inbred C57BL
Mice, Transgenic
Orthomyxoviridae Infections - pathology
Parenchyma
Protein C
Pulmonary Alveoli - pathology
Pulmonary Alveoli - physiopathology
Regeneration
Respiratory function
Ring structures
Stem cells
Structural damage
Surface active agents
Surfactant protein C
Uteroglobin - metabolism
Viruses
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Summary:Regeneration of alveolar epithelia following severe pulmonary damage is critical for lung function. We and others have previously shown that Scgb1a1-expressing cells, most likely Clara cells, can give rise to newly generated alveolar type 2 cells (AT2s) in response to severe lung damage induced by either influenza virus infection or bleomycin treatment. In this study, we have investigated cellular pathway underlying the Clara cell to AT2 differentiation. We show that the initial intermediates are bronchiolar epithelial cells that exhibit Clara cell morphology and express Clara cell marker, Scgb1a1, as well as the AT2 cell marker, pro-surfactant protein C (pro-SPC). These cells, referred to as pro-SPC(+) bronchiolar epithelial cells (or SBECs), gradually lose Scgb1a1 expression and give rise to pro-SPC(+) cells in the ring structures in the damaged parenchyma, which appear to differentiate into AT2s via a process sharing some features with that observed during alveolar epithelial development in the embryonic lung. These findings suggest that SBECs are intermediates of Clara cell to AT2 differentiation during the repair of alveolar epithelia following severe pulmonary injury.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0071028