Differential expression of VEGF mRNA splice variants in newborn and adult hyperoxic lung injury

1 Division of Neonatology, Department of Pediatrics, Strong Children's Research Center, University of Rochester School of Medicine, Rochester 14642; and 2 Department of Pharmacology and Toxicology, State University of New York at Buffalo, Buffalo, New York 14214 Lung development and repair of hyperoxic injury require closely regulated growth and regeneration of alveolar capillaries. Vascular endothelial growth factor (VEGF), a mitogen for endothelial cells, is expressed by alveolar epithelial cells. Alternative splicing of VEGF mRNA results in isoforms of varying mitogenicity and solubility. We examined changes in the proportions of the VEGF splice variant mRNAs in rabbit lung development and in control, oxygen-injured, and recovering newborn and adult rabbit lungs. The proportion of the 189-amino acid VEGF mRNA, which codes for an isoform that binds to the extracellular matrix, increased fivefold during development (from 8% of total VEGF message at 22 days gestation to 40% in 10-day newborn lungs; P