Bombesin-like peptide receptor gene expression, regulation, and function in fetal murine lung
Bombesin-like peptide receptor gene expression, regulation, and function in fetal murine lung
复制标题
DOI：
10.1152/ajplung.00436.2002
复制
发表时间：
2004-01-01
影响因子：
4.9
通讯作者：
Sunday, ME
中科院分区：
文献类型：
--
作者：
Shan, L;Emanuel, RL;Sunday, ME
蛙皮素样肽（BLP）免疫反应性在胎儿肺中以高水平发生。先前的研究表明蛙皮素促进胎儿肺发育。为了检验这种作用是由已知的哺乳动物蛙皮素受体[胃泌素释放肽（GRP）/蛙皮素偏好受体（GRPR）、神经介肽B（NMB）受体（NMBR）和孤儿蛙皮素受体亚型3（BRS-3）]介导的假设，我们分析了小鼠肺中GRPR、NMBR和BRS-3基因表达的个体发生。我们研究了地塞米松和蛙皮素对这三个基因的调节作用，这两种基因调节肺的发育。通过掺入[H-3]胸苷和[H-3]胆碱，我们评估了GRP、NMB和Leu（8）-叶绿酸是否调节胎肺外植体中的肺生长和成熟。GRPR基因的表达主要在子宫内检测到，而NMBR和BRS-3基因的表达从胚胎的第13 - 16天和出生后的多天。所有三种mRNA都存在于气道上皮细胞和间充质细胞中，但以不同的相对模式出现。这些基因受到不同的调控。地塞米松和蛙皮素增加GRPR mRNA，蛙皮素下调NMBR，没有代理商影响BRS-3。GRP增加外植体中[H-3]胸苷和[H-3]胆碱的掺入，而NMB诱导细胞增殖，Leu（8）-叶绿酸产生不同的结果。累积的数据表明，参与多种BLP受体，包括新的分子，并反对简单的功能冗余在肺发育过程中，这个基因家族。
Bombesin-like peptide (BLP) immunoreactivity occurs at high levels in fetal lung. Previous studies showed that bombesin promotes fetal lung development. To test the hypothesis that such effects are mediated by known mammalian bombesin receptors [gastrin-releasing peptide (GRP)/bombesin-preferring receptor (GRPR), neuromedin B (NMB) receptor (NMBR), and the orphan bombesin receptor subtype-3 (BRS-3)], we analyzed the ontogeny of GRPR, NMBR, and BRS-3 gene expression in mouse lung. We examined the regulation of these three genes by dexamethasone and bombesin, which modulate lung development. Using incorporation of [H-3] thymidine and [H-3] choline, we then assessed whether GRP, NMB, and Leu(8)-phyllolitorin modulate lung growth and maturation in fetal lung explants. GRPR gene expression was detected predominantly in utero, whereas NMBR and BRS-3 genes were expressed from embryonic days 13 - 16 and on multiple postnatal days. All three mRNAs are present in airway epithelium and mesenchymal cells but occur in different relative patterns. These genes were regulated differently. Dexamethasone and bombesin increased GRPR mRNA, bombesin downregulated NMBR, and neither agent affected BRS-3. GRP increased incorporation of [H-3] thymidine and [H-3] choline in explants, whereas NMB induced cell proliferation and Leu(8)-phyllolitorin yielded variable results. Cumulative data suggest the involvement of multiple BLP receptors, including novel molecules, and argue against simple functional redundancy within this gene family during lung development.