A schematic for the proposed mechanism for the effects noted in our experimental models is shown. Hyperoxia exposure to the developing murine lung acts on alveolar epithelial cells and interstitial fibroblasts to increase TGF-β1. In alveolar epithelial cells, this leads to increased CTGF and activation of the Fas-L and caspase-3 mediated cell death pathway. In the alveolar interstitial fibroblasts, TGF-β1 enhances myofibroblast transdifferentiation. The combined effect of increased cell death and myofibroblast transdifferentiation leads to impaired alveolarization, resulting in the pulmonary phenotype of larger, simplified alveoli, mimicking human bronchopulmonary dysplasia. JNK pathway inhibition impacts on downstream effects as shown in the figure. TGF-β1: transforming growth factor beta; JNKi: JNK inhibitor; CTGF: connective tissue growth factor; Fas-L: Fas-ligand.
Li et al. BMC Cell Biology 2011 12:54 doi:10.1186/1471-2121-12-54