title: The lung alveolar lipofibroblast: an evolutionary strategy against neonatal hyperoxic lung injury.
abstract: CONCLUSIONS
  Oxygen, the main mode of support for premature infants with immature lungs, can cause toxicity by producing reactive oxygen species (ROS) that disrupt homeostasis; yet, these same molecules were entrained to promote vertebrate lung phylogeny. By providing a deeper understanding of this paradox, we propose physiologically rational strategies to prevent chronic lung disease (CLD) of prematurity.
  
  
  BACKGROUND
  To prevent neonatal hyperoxic lung damage biologically, we have exploited the alveolar defense mechanism(s) that evolutionarily evolved to combat increased atmospheric oxygen during the vertebrate water to land transition.
  
  
  RESULTS
  Over the course of vertebrate lung evolution, ROS promoted the formation of lipofibroblasts, specialized adepithelial cells, which protect the alveoli against oxidant injury; peroxisome proliferator-activated receptor gamma (PPARγ), the master switch for lipofibroblast differentiation, prevents such oxidant lung injury, both by directly promoting mesodermal differentiation and its antioxidant defenses, and indirectly by stimulating the developmental epithelial-mesenchymal paracrine interactions that have physiologically determined lung surfactant production in accord with the lung's phylogenetic adaptation to atmospheric oxygen, preventing Respiratory Distress Syndrome at birth.
  
  
  CONCLUSIONS
  The molecular strategy (PPARγ agonists) to prevent CLD of prematurity, proposed by us, although seems to be robust, effective, and safe under experimental conditions, it awaits detailed pharmacokinetic and pharmacodynamic studies for its safe and effective clinical translation to human infants. Antioxid. Redox Signal. 21, 1893-1904. "I have procured air [oxygen]…between five and six times as good as the best common air that I have ever met with." -Joseph Priestley, 1775.
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center , Torrance, California.
authors.forename: Virender K
authors.initials: VK
authors.lastname: Rehan
authors.forename: John S
authors.initials: JS
authors.lastname: Torday
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005347:Fibroblasts / Q000473:pathology / Q000502:physiology*; D006801:Humans; D018496:Hyperoxia / Q000473:pathology* / Q000503:physiopathology*; D007231:Infant, Newborn; D011650:Pulmonary Alveoli / Q000473:pathology / Q000502:physiology*