Differential Expression of Cyclic Nucleotide Phosphodiesterases 4 in Developing Rat Lung Running Title: PDE4 in developing rat lung

During the perinatal period, lungs undergo changes to adapt to air breathing. The genes involved in these changes are developmentally regulated by various signaling pathways, including the cyclic nucleotide cAMP. As PDE4s are critical enzymes for regulation of cAMP levels, the objective of this study was to investigate PDE4s ontogeny in developing rat lung during the perinatal period. Pulmonary PDE4 activity, PDE4A-D and PDE4B and PDE4D variants expression levels, PDE4B and PDE4D protein levels, and PDE4Ds localization in distal lung were determined. PDE4 activity increased towards term, dropped at birth, and increased thereafter to reach a plateau at the end of the second week of life. PDE4B2 and PDE4D long forms demonstrated a pattern of expression that increased markedly at birth. After birth, PDE4D were expressed in alveolar epithelial and mesenchymal cells. The study therefore evidenced striking variations in expression patterns among the PDE4 family that differed from changes in global PDE4 activity.