Thyroid transcription factor-1 influences the early phase of compensatory lung growth in adult mice

Rationale: Compensatory lung growth has been well described as a phenomenon in many animal models, but still little is known about the nature, extent, and modulation of such growth. We hypothesized that compensatory lung growth may at least in part recapitulate developmental lung growth, and factors known to be important during normal lung development, such as thyroid transcription factor 1 (TTF-1), may be reactivated during compensatory lung growth. Objectives: To investigate the role of TTF-1 in correlation with the morphological changes during compensatory lung growth. Methods: Sequential changes in TTF-1 expression and morphology were examined in the residual right lung after left pneumonectomy in 9-week-old mice. The effect of temporary knockdown of TTF-1 on compensatory lung growth was also evaluated. Measurements and Main Results: TTF-1 was transiently but significantly elevated at an early stage in compensatory lung growth. Morphologically, a process resembling septation in lung development may have been initiated during this period in the vicinity of the alveolar duct. Furthermore, temporary knockdown of TTF-1 transiently but significantly delayed the early phase of compensatory lung growth. Conclusions: These results indicate the influential role of TTF-1 in modulating, and possibly initiating, the early phase of compensatory lung growth. Morphologically, compensatory lung growth may at least in part resemble developmental growth.