TRANSIENT ELEVATION OF MESSENGER-RNA ENCODING GASTRIN-RELEASING PEPTIDE, A PUTATIVE PULMONARY GROWTH-FACTOR IN HUMAN-FETAL LUNG
TRANSIENT ELEVATION OF MESSENGER-RNA ENCODING GASTRIN-RELEASING PEPTIDE, A PUTATIVE PULMONARY GROWTH-FACTOR IN HUMAN-FETAL LUNG
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DOI：
10.1172/jci113176
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发表时间：
1987-10-01
影响因子：
15.9
通讯作者：
CHIN, WW
中科院分区：
文献类型：
--
作者：
SPINDEL, ER;SUNDAY, ME;CHIN, WW
胃泌素释放肽（GRP）是两栖动物肽铃蟾肽的哺乳动物同源物，存在于肺神经内分泌细胞中，并且似乎是正常和肿瘤肺细胞的生长因子。此前我们报道了编码人类 GRP 的信使 RNA (mRNA) 和基因的克隆。我们现在报道，在肺发育的小管阶段（大约妊娠 16 至 30 周），人胎肺中的 GRP mRNA 显着升高。通过RNA印迹和原位杂交分析，在9-10周时首次在胎儿肺中检测到GRP mRNA，从16周到大约10周，其水平稳定在成人肺中的25倍。妊娠 30 周后，到妊娠 34 周时下降至接近成人水平。相比之下，GRP 肽水平一直保持升高状态，直到出生后几个月。与此相一致的是，原位杂交和免疫组织化学研究表明，GRP mRNA 和肽始终共定位于妊娠早期肺中，但在新生儿肺中，许多含有 GRP 肽的细胞不再含有 GRP mRNA。 .apprx 期间高水平 GRP mRNA 的瞬时表达。胎儿肺发育的 12 周阶段表明，肺神经内分泌细胞分泌的 GRP 或其 COOH 末端肽可能在正常肺发育中发挥作用。
Gastrin-releasing peptide (GRP), the mammalian homologue of the amphibian peptide bombesin, is present in pulmonary neuroendocrine cells and appears to be a growth factor for both normal and neoplastic pulmonary cells. Previously we have reported the cloning of the messenger RNAs (mRNAs) and gene that encode human GRP. We now report that GRP mRNAs are markedly elevated in human fetal lung during the canalicular phase of pulmonary development (from .apprx. 16 to 30 wk gestation). By RNA blot and in situ hybridization analyses, GRP mRNAs were first detectable in fetal lung at 9-10 wk, plateaued at levels 25-fold higher than in adult lungs from 16 to .apprx. 30 wk and then declined to near adult levels by 34 wk gestation. By contrast, GRP peptide levels remain elevated until several months after birth. Consistent with this, in situ hybridization and immunohistochemical studies showed that GRP mRNA and peptide consistently colocalized in early gestation lung but that in neonatal lung, many cells that contained GRP peptide no longer contained GRP mRNA. The transient expression of high levels of GRP mRNAs during an .apprx. 12-wk phase of fetal lung development suggests that the secretion of GRP or its COOH-terminal peptides from pulmonary neuroendocrine cells may play a role in normal lung development.