Maturational Factors Modulate Transcription Factors CCAAT/Enhancer-Binding Proteins , , , and Peroxisome Proliferator–Activated Receptor- in Fetal Rat Lung Epithelial Cells

Previous investigations have evidenced the importance of CCAAT/enhancer-binding proteins (C/EBPs) and peroxisome proliferator–activated receptor (PPAR) for lung development, especially for alveolar type II cells (ATII). This prompted us to explore whether ATII maturation-promoting mediators controlled their expression in isolated ATII. In whole rat lung, C/EBP , , , and PPAR mRNAs increased 3–5 times between gestational day 18 and term (Day 22), dropped around birth, then reincreased. C/EBP and , but not PPAR , displayed similar profile in isolated ATII; C/EBP transcript disappeared and the protein became hardly detectable in isolated cells. In cultured ATII, dexamethasone increased C/EBP and PPAR mRNAs 2–4 times, and cyclic AMP increased C/EBP and mRNAs 1.5 times. Whereas retinoic acid increased C/EBP and PPAR mRNAs 1.5 times in ATII in vitro, vitamin-A deficiency strongly decreased fetal lung C/EBP , , and PPAR transcripts in vivo. C/EBP , , and PPAR mRNAs were also increased in vitro by epidermal growth factor and keratinocyte growth factor, whereas they were unchanged by the maturation inhibitor transforming growth factor. C/EBP expression was not reinduced by any mediator. Changes in transcripts were reflected in protein levels analyzed through Western blotting. These results argue for a role of these factors in ATII functional maturation, and indicate a multifactorial control of their ontogeny.