Role of Type II Alveolar Epithelial Cell Transcription Factor FoxM1 in the Repair of Alveolar Epithelial Barrier.

The repair of the alveolar epithelial barrier is essential for the restoration of normal gas exchange function and homeostasis after lung injury. The normal alveolar epithelium is composed of two types of cells: flat type I cells comprising ∼95% of the gas-exchange surface, and cuboidal type II cells, which secrete surfactant. Upon alveolar injury, some or all of the type II cells proliferate and trans-differentiate into type I cells, thus repairing the epithelial barrier. However, molecular mechanisms of this process are unknown. Here, we utilized a mouse model of lung injury caused by it. Pseudomonas aeruginosa (PA) infection. We observed that the expression of FoxM1, a forkhead transcription factor regulating epithelial cell proliferation, was increased 3-fold specifically in type II cells at 72h post infection, coincident with the cell proliferation phase and preceding the re-annealing of alveolar barrier. To investigate the role of FoxM1, we utilized an alveolar type II cell specific FoxM1 knock-out mouse line. We observed decreased cell proliferation as well as defective alveolar epithelial barrier repair after PA challenge of mice with the mutant background. These findings suggest a critical role of transcription factor FoxM1 in alveolar epithelial barrier repair and mediating the transition from type II to type I cells required for barrier re-annealing. [ABSTRACT FROM AUTHOR]