CD10/NEUTRAL ENDOPEPTIDASE 24 11 REGULATES FETAL LUNG GROWTH AND MATURATION INUTERO BY POTENTIATING ENDOGENOUS BOMBESIN-LIKE PEPTIDES
CD10/NEUTRAL ENDOPEPTIDASE 24 11 REGULATES FETAL LUNG GROWTH AND MATURATION INUTERO BY POTENTIATING ENDOGENOUS BOMBESIN-LIKE PEPTIDES
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DOI：
10.1172/jci116417
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发表时间：
1993-05-01
影响因子：
15.9
通讯作者：
SUNDAY, ME
中科院分区：
文献类型：
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作者：
KING, KA;HUA, J;SUNDAY, ME
铃蟾肽样肽 (BLP) 是支气管上皮细胞和小细胞肺癌的有丝分裂原，可促进胎儿肺在子宫内和器官培养物中的生长和成熟。 BLP 被 CD10/中性内肽酶 24.11 (CD10/NEP) 水解，该酶在支气管上皮中表达，具有抑制 BLP 介导的小细胞肺癌生长的作用。为了确定 CD10/NEP 是否调节肽介导的肺发育，我们对妊娠期 e15-17 的子宫内胎儿小鼠施用了一种特定的 CD10/NEP 抑制剂 SCH32615。在 e18 上评估胎儿肺组织的以下方面：（a）使用[H-3]胸苷掺入核 DNA 进行生长； (b) 成熟使用：[H-3]胆碱掺入表面活性剂磷脂，II型肺细胞的电子显微镜检查，以及表面活性剂脱辅基蛋白A、B和C的Northern印迹分析。抑制CD10/NEP刺激[H-3]胸苷掺入DNA（高于基线70%，P<0.005），[H-3]胆碱掺入表面活性剂磷脂（38%）高于基线，P < 0.005），II 型肺细胞数量增加（高于基线 36%，P = 0.07），表面活性剂蛋白 A 转录物增加五倍（P < 0.05）。 CD10/NEP 介导的作用可被特异性铃蟾肽受体拮抗剂 [D-Phe12, Leu14]铃蟾肽完全阻断。这些观察结果表明 CD10/NEP 调节内源性 BLP 介导的胎儿肺生长和成熟。
Bombesin-like peptides (BLPs) are mitogens for bronchial epithelial cells and small cell lung carcinomas, and increase fetal lung growth and maturation in utero and in organ cultures. BLPs are hydrolyzed by the enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) which is expressed in bronchial epithelium and functions to inhibit BLP-mediated growth of small cell lung carcinomas. To determine whether CD10/NEP regulates peptide-mediated lung development, we administered a specific CD10/NEP inhibitor, SCH32615, to fetal mice in utero from gestational days e15-17. Fetal lung tissues were evaluated on e18 for: (a) growth using [H-3]thymidine incorporation into nuclear DNA; and (b) maturation using: [H-3]choline incorporation into surfactant phospholipids, electron microscopy for type II pneumocytes, and Northern blot analyses for surfactant apoproteins A, B, and C. Inhibition of CD10/NEP stimulated [H-3]thymidine incorporation into DNA (70% above baseline' P < 0.005), [H-3]choline incorporation into surfactant phospholipids (38% above baseline, P < 0.005), increased numbers of type II pneumocytes (36% above baseline, P = 0.07), and fivefold higher surfactant protein A transcripts (P < 0.05). CD10/NEP-mediated effects were completely blocked by the specific bombesin receptor antagonist, [D-Phe12, Leu14]bombesin. These observations suggest that CD10/NEP regulates fetal lung growth and maturation mediated by endogenous BLPs.