Maturational factors modulate transcription factors CCAAT/enhancer-binding proteins alpha, beta, delta, and peroxisome proliferator-activated receptor-gamma in fetal rat lung epithelial cells.
Maturational factors modulate transcription factors CCAAT/enhancer-binding proteins alpha, beta, delta, and peroxisome proliferator-activated receptor-gamma in fetal rat lung epithelial cells.
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发表时间：
2003
影响因子：
6.4
通讯作者：
A. Barlier-Mur;B. Chailley‐Heu;C. Pinteur;A. Henrion-Caude;C. Delacourt;J. Bourbon
中科院分区：
文献类型：
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作者：
A. Barlier-Mur;B. Chailley‐Heu;C. Pinteur;A. Henrion-Caude;C. Delacourt;J. Bourbon
先前的研究已经证明了CCAAT/增强子结合蛋白（C/EBP）和过氧化物酶体增殖物激活受体（PPAR）γ对肺发育的重要性，特别是对肺泡II型细胞（ATII）。这促使我们探索ATII促成熟介质是否控制其在孤立ATII中的表达。在整个大鼠肺中，C/EBPalpha、β、δ和PPARgamma mRNA在妊娠第18天和足月（第22天）之间增加3-5倍，在出生前后下降，然后重新增加。C/EBP β和δ，而不是PPARgamma，在分离的ATII中显示出相似的特征; C/EBP α转录物消失，并且在分离的细胞中蛋白质变得几乎检测不到。在培养的ATII中，地塞米松使C/EBP β和PPARgamma mRNA增加2-4倍，环AMP使C/EBP β和δ mRNA增加约1.5倍。而维甲酸增加C/EBP β和PPARgamma mRNA的1.5倍ATII在体外，维生素A缺乏症强烈降低胎肺C/EBP α，β，和PPARgamma转录在体内。C/EBP β，δ和PPARgamma的mRNA也增加了体外表皮生长因子和角质形成细胞生长因子，而他们不变的成熟抑制剂转化生长因子-β。C/EBPalpha的表达没有被任何介质重新诱导。通过Western印迹分析，转录物的变化反映在蛋白质水平上。这些结果表明这些因素在ATII功能成熟中的作用，并表明其个体发育的多因素控制。
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.