Epithelial‐Mesenchymal Transition Is Not Critical In The Pathogenesis of The Chronic Lung Disease of The Premature Infant

Abstract

Although Epithelial‐Mesenchymal Transition (EMT) in response to lung injury has been recently reported in the adult lung, its role in the Chronic Lung Disease (CLD) of the premature infant is not known. We examined whether fetal rat alveolar type II cells (ATII) undergo EMT in response to cytokines that are known to induce EMT of the adult ATII. Fetal rat (Sprague Dawley) lung ATII at embryonic day (e)19 were maintained in culture with and without TGFβ 1 (2.5 ng/ml), TNFα (1 ng/ml), and TGFβ 1 (2.5 ng/ml) + TNFα (1 ng/ml) for up to 10 days. EMT was determined by the expression of well established markers of the alveolar epithelial (Surfactant Protein C, CTP:cholinephosphate cytidylyltransferase α, and aquaporin‐5) and mesenchymal (α Smooth Muscle Actin and calponin) phenotypes on days 1, 6, and 10 at mRNA and protein levels along with the functional assessment of ATII function by their capacity to synthesize saturated phosphatidylcholine. There was no evidence of either spontaneous or cytokine‐stimulated EMT up to 10 days in culture in e19 rat ATII cells. Further, on cytokine stimulation, there was a dramatic increase in bone morphogenetic protein‐7 expression, a transcription factor that is known to block EMT. We conclude that premature ATII cells are resistant to EMT and unlike the pathogenesis of pulmonary fibrosis in the adult, EMT is not a prominent feature of CLD in the premature infant. Funding‐NIH HL75405 & HL55268).