Maturational factors modulate transcription factors CCAAT/enhancer-binding proteins alpha, beta, delta, and peroxisome proliferator-activated receptor-gamma 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)gamma 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/EBPalpha, beta, delta, and PPARgamma mRNAs increased 3-5 times between gestational day 18 and term (Day 22), dropped around birth, then reincreased. C/EBPbeta and delta, but not PPARgamma, displayed similar profile in isolated ATII; C/EBPalpha transcript disappeared and the protein became hardly detectable in isolated cells. In cultured ATII, dexamethasone increased C/EBPbeta and PPARgamma mRNAs 2-4 times, and cyclic AMP increased C/EBPbeta and delta mRNAs approximately 1.5 times. Whereas retinoic acid increased C/EBPbeta and PPARgamma mRNAs 1.5 times in ATII in vitro, vitamin-A deficiency strongly decreased fetal lung C/EBPalpha, beta, and PPARgamma transcripts in vivo. C/EBPbeta, delta, and PPARgamma 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-beta. C/EBPalpha 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.
Inserm U 492, Faculté de Médecine, 8 rue du Général Sarrail, 94010 Créteil cedex, France.
Anne-Marie
AM
Barlier-Mur
Bernadette
B
Chailley-Heu
Claudie
C
Pinteur
Alexandra
A
Henrion-Caude
Christophe
C
Delacourt
Jacques R
JR
Bourbon
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D008168:Lung / Q000378:metabolism*; D008297:Male; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014802:Vitamin A Deficiency / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors