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Cellular Plasticity in Lung Injury and Repair
Published in the Proceedings of the American Thoracic Society, Vol 8. pp 215-222, 2011, http://pats.atsjournals.org/
Definition of Cell Plasticity: The ability of some cells to switch from one specific program of gene expression (phenotype) to another in response to specific signals from the environment in a regulated manner. The changes may be reversible or irreversible and may or may not involve changes in cell shape, adhesion and proliferation.
Recent observations suggest that epithelial cells are inherently plastic. The most extreme example of this plasticity, first recognized in the 1970’s, is the process of epithelial to mesenchymal transition (EMT). More commonly, epithelial cells lose epithelial characteristics and become migratory, but do not acquire mesenchymal marker expression. Alternatively, epithelial cells transiently convert to a mesenchymal shape without losing epithelial marker expression. These observations suggest that a spectrum of epithelial plasticity changes can occur, resulting in downregulation of epithelial differentiation and integrity to different extents, and in changes that may or may not qualify as EMT.
The realization that epithelial cells are not only a target for injury leading to fibrosis but a critical driver of the pathobiology has stimulated interest to find therapeutic modalities that interfere with epithelial signaling driving mesenchymal expansion and EMT including strategies to promote epithelial survival.
Recognizing the relationship of cell and molecular events on lung health and disease, the National Heart, Lung, and Blood Institute (NHLBI) convened extramural experts, from many disciplines (lung development, cell biology, stem/progenitor cell biology, lung injury, and lung cancer), at a Workshop “Cellular Plasticity in Lung Injury and Repair” on April 19-20, 2010.
The objective of the workshop was: 1) To review the state of science in cellular plasticity in the lung; 2) To make recommendations to the Institute to fill gaps; 3) To prioritize new research directions; and, 4) To capitalize on scientific opportunities. Experts from multiple fields participated, who made recommendations that could facilitate translation of basic research findings into practice to better diagnose, treat, and prevent irreversible lung remodeling in diseases such as idiopathic pulmonary fibrosis and bronchopulmonary dysplasia. The priority areas identified for research in cell plasticity in lung injury and repair included: 1) epithelial plasticity, 2) control of plasticity, 3) fibroblast plasticity and cross-talk, and 4) translation to human disease.
Working Group Members
NHLBI, Division of Lung Division Staff
National Institute of Diabetes, Digestion, and Kidney
Last Updated: June 2011