Examining the Role of Notch Signaling in Dysplastic Lung Repair

Severe lung injury promotes the appearance of ectopic basal cells in the alveolar space. Since these cells appear to contribute to barrier restoration but demonstrate very inefficient differentiation into normal alveolar epithelium, this represents a dysplastic repair response. Prior work demonstrated the necessity of Notch signaling for expansion of these cells directly and indirectly via interactions with activated fibroblasts, but the original studies largely relied on γ-secretase inhibitors which lack specificity for the Notch pathway. Here we use transgenic mice expressing a dominant-negative MAML construct to confirm that Notch signaling to dysplastic cells impacts their expansion post-influenza. However, Notch inhibition at later time points did not appreciably increase differentiation into alveolar epithelial cells. These results confirm earlier studies and reiterate the advantages of genetic approaches to directly inhibit Notch over less specific pharmacological approaches.