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

Inserm U 492, Faculté de Médecine, Université Paris XII, Créteil; and Inserm E 213, Hôpital Trousseau Assistance Publique-Hopitaux de Paris, Paris, France

Address correspondence to: J. R. Bourbon, Inserm U 492, Faculté de Médecine, 8 rue du Général Sarrail, 94010 Créteil cedex, France. E-mail: Jacques.Bourbon{at}creteil.inserm.fr

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, ß, , and PPAR mRNAs increased 3–5 times between gestational day 18 and term (Day 22), dropped around birth, then reincreased. C/EBPß 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/EBPß and PPAR mRNAs 2–4 times, and cyclic AMP increased C/EBPß and mRNAs 1.5 times. Whereas retinoic acid increased C/EBPß and PPAR mRNAs 1.5 times in ATII in vitro, vitamin-A deficiency strongly decreased fetal lung C/EBP, ß, and PPAR transcripts in vivo. C/EBPß, , 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-ß. 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.

Abbreviations: alveolar type II cells, ATII • CCAAT/enhancer-binding protein, C/EBP • dexamethasone, Dex • Dulbecco's modified Eagle's medium, DMEM • epidermal growth factor, EGF • Engelbreth-Holm-Swarm, EHS • fetal bovine serum, FBS • keratinocyte growth factor, KGF • peroxisome proliferator–activated receptor, PPAR • retinoic acid (all trans), RA • surfactant protein, SP • transforming growth factor, TGF • vitamin A–deficient, VAD

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