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1 Lung Biology, Georgetown University School of Medicine, Washington, District of Columbia, United States
2 Research Center for Genetic Medicine, Children's National Medical Center, Washington, District of Columbia, United States
3 Lung Biology, Georgetown University, Washington, District of Columbia, United States
* To whom correspondence should be addressed. E-mail: massarod{at}georgetown.edu.
Alveolar regenerative gene expression is unidentified partly because its onset, after a regenerative stimulus, is unknown. Toward addressing this void, we used a mouse model in which calorie restriction produces alveolar loss, and ad libitum access to food after calorie restriction induces alveolar regeneration. We selected four processes (cell replication, angiogenesis, extracellular matrix remodeling, and guided cell motion) that would be required to convert a flat segment of alveolar wall into a septum that increases gas-exchange surface area. Global gene expression in lung supportive of processes required to form a septum was present within three hours of allowing calorie restricted mice food ad libitum. One hour after providing calorie restricted mice food ad libitum, RNA level expression supportive of cell replication was present, with little evidence of expression supportive of angiogenesis, extracellular matrix remodeling, or guided cell motion. Cell replication was more directly assayed by measuring DNA synthesis in lung. This measurement was made three hours after allowing calorie restricted mice food ad libitum because translation may be delayed. Ad libitum food intake, following calorie restriction, elevated DNA synthesis. Thus, RNA expression one hour after allowing calorie restricted mice food ad libitum supported increased cell replication; measurements at three hours revealed increased DNA synthesis, and RNA expression, supportive of the three other processes required to form a septum. These findings identify the first hour after providing calorie restricted mice ad libitum access to food, as the onset of gene expression in this model that supports processes needed for alveolar regeneration.
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