Abstract
SIGNIFICANCE: Fetal lung development takes place in hypoxia meaning that premature birth is hyperoxia for the prematurely born infant. The most common respiratory morbidity afflicting premature infants is bronchopulmonary dysplasia (BPD). Pathophysiologically, BPD represents the impact of injury, including O2 toxicity, to the immature developing lung that causes arrested lung development. RECENT ADVANCES: The thioredoxin (Trx) system, which is predominantly expressed in pulmonary epithelia in the newborn lung, acts as an antioxidant system; however, it is increasingly recognized as a key redox regulator of signal transduction and gene expression via thiol-disulfide exchange reactions. CRITICAL ISSUES: This review focuses on the contribution of Trx family proteins toward normal and aberrant lung development, in particular, the roles of the Trx system in hyperoxic responses of alveolar epithelial cells, aberrant lung development in animal models of BPD, O2-dependent signaling processes, and possible therapeutic efficacy in preventing O2-mediated lung injury. FUTURE DIRECTIONS: The significant contribution of the Trx system toward redox regulation of key developmental pathways necessary for proper lung development suggests that therapeutic strategies focused on preserving pulmonary Trx function could significantly improve the outcomes of prematurely born human infants.