Methionine’s Role in Hyperoxia-Induced Pulmonary Dysplasia


  • N Nisen Indiana University School of Medicine
  • D Ranasinghe Indiana University School of Medicine
  • M Schwarz Indiana University School of Medicine


Background/Objective: Following preterm birth in the saccular stage of lung development, 24 weeks gestational age to term, infants are forced to navigate the further development of their lungs with the abnormal environmental influences of oxygen. This disruption of normal development of alveoli is the etiology of bronchopulmonary dysplasia (BPD), which is a chronic pulmonary disease of preterm infants. We hypothesize that this lung dysplasia is based upon the disruption of the role of one of the lung metabolites, Methionine, that is utilized during this period. Specifically, we postulate that Methionine’s role in this dysplasia could be used as a rescue of normal lung development if undeterred.

Methods: Endothelial Colony Forming Cells (ECFCs) were utilized to measure angiogenesis in vitro in the presence of a variety of concentrations of Methionine. A WST-1 Assay, Crystal Violet Assay, and Scratch Assays were performed to quantify the amount of ECFC proliferation and migration in the presence/absence of Methionine. Western blotting analysis was performed to measure the expression of enzymes of the one carbon metabolism pathway. A murine model was utilized to contrast methionine’s dietary role lung development in hyperoxia and normal oxygen conditions.

Results: We have seen that the presence of Methionine increases endothelial cell proliferation and migration. We found that the expression of the enzymes in the one carbon metabolism pathway are significantly impacted by the presence of Methionine. Histological studies have further shown Methionine’s role as a rescue of hyperoxia induced alveolar dysplasia, identifying Methionine as a crucial metabolite in lung development.

Conclusion and Clinical Implications: Through these studies, we believe that new therapeutic targets are elicited that will guide and improve the ability to improve lung development of a premature infant.






Indiana Medical Student Program for Research and Scholarship Award Recipients