Shan Lin, Emanuel Rodica L, Dewald Denise, Torday John S, Asokanathan Nithiananthan, Wada Keiji, Wada Etsuko, Sunday Mary E
Department of Pathology, Children's and Brigham and Women's Hospitals and Harvard Medical School, Boston, MA 02115, USA.
Am J Physiol Lung Cell Mol Physiol. 2004 Jan;286(1):L165-73. doi: 10.1152/ajplung.00436.2002. Epub 2003 Sep 5.
Bombesin-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 [3H]thymidine and [3H]choline, we then assessed whether GRP, NMB, and Leu8-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 [3H]thymidine and [3H]choline in explants, whereas NMB induced cell proliferation and Leu8-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.
蛙皮素肽（BLP）免疫反应性在胎儿肺中高水平存在。先前的研究表明蛙皮素可促进胎儿肺发育。为了验证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）/蛙皮素优先受体（GRPR）、神经降压素B（NMB）受体（NMBR）和孤儿蛙皮素受体亚型3（BRS - 3）]介导的这一假设，我们分析了小鼠肺中GRPR、NMBR和BRS - 3基因表达的个体发生情况。我们研究了地塞米松和蛙皮素对这三个基因的调控，它们可调节肺发育。然后，我们使用[3H]胸腺嘧啶核苷和[3H]胆碱掺入法，评估GRP、NMB和亮氨酸8 - 叶泡蛙皮素是否调节胎儿肺外植体的肺生长和成熟。GRPR基因表达主要在子宫内被检测到，而NMBR和BRS - 3基因在胚胎第13 - 16天以及出生后的多个日子表达。所有三种mRNA都存在于气道上皮和间充质细胞中，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，而这两种药物均不影响BRS - 3。GRP增加外植体中[3H]胸腺嘧啶核苷和[3H]胆碱的掺入，而NMB诱导细胞增殖，亮氨酸8 - 叶泡蛙皮素产生不同的结果。累积数据表明多种BLP受体参与其中，包括新分子，并反对该基因家族在肺发育过程中存在简单的功能冗余。
