The Hyperoxia-Mediated Decrease In Tenascin-C In Fetal Lung Fibroblasts Inhibits Cell Migration

Hyperoxic exposure is associated with the arrested alveolarization characteristic of bronchopulmonary dysplasia (BPD). The myofibroblast is required for normal alveolarization and synthesizes important extracellular matrix (ECM) proteins. In a reciprocal manner, this ECM modulates fibroblast function. To investigate the link between ECM and lung myofibroblast migration, we tested the hypothesis that hyperoxia inhibits fetal lung fibroblast TN‐C expression, leading to a reduction in cell migration. Primary fetal lung fibroblasts were maintained at fetal O 2 tension (3% O 2 ) and transitioned to hyperoxia (21%, 40%, and 65% O 2 ) for 48 hours. Hyperoxia exposure reduced TN‐C protein expression in a dose‐dependent manner, with a >10‐fold decrease in TN‐C protein in fibroblasts grown in 65% O 2 . In contrast, the ECM protein fibronectin (FN) was unchanged by hyperoxia exposure. Functionally, the hyperoxia‐mediated decrease in TN‐C was accompanied by a 40% reduction in cell migration. We speculate that the anti‐adhesive properties of TN‐C promote fibroblast migration in the developing lung, and hyperoxia‐induced loss of TN‐C inhibits this migration by promoting cell adhesion.