Peroxisome Proliferator-Activated Receptor γ Agonists Enhance Lung Maturation in a Neonatal Rat Model

The nuclear transcription factor peroxisome proliferator-activated receptor (PPAR) gamma plays a central role in normal lung development. However, the effects of modulating PPAR-gamma expression by exogenously administered PPAR-gamma agonists on lung development and basic blood biochemical and metabolic profiles in a developing animal are not known. To determine these effects, newborn Sprague-Dawley rat pups were administered either diluent or rosiglitazone (RGZ), a potent PPAR gamma agonist. for either 1 or 7 d. Then the pups were killed and the lungs were examined for specific markers of alveolar epithelial, mesenchymal. and vascular maturation, and lung morphometry. The effect of RGZ on a limited number of blood biochemical and metabolic parameters was also determined. Overall, systemically administered RGZ significantly enhanced lung maturation without affecting serum electrolytes, blood glucose, blood oases, plasma cholesterol. triglycerides. and serum cardiac troponin levels. The lung maturation effect of PPAR-gamma agonists was also confirmed by another PPAR-gamma agonist, the naturally occurring PPAR-gamma ligand prostaglandin J(2). We conclude that systemically administered RGZ significantly enhances lung maturation without significantly affecting the acute blood biochemical and metabolic profiles. providing rationale for further Studying PPAR-gamma agonists for enhancing lung maturation. and for promoting lung injury/repair in neonates. (Pediatr Res 65: 150-155, 2009)