Department of Neonatology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China.
Mol Med Rep. 2018 Apr;17(4):5988-5995. doi: 10.3892/mmr.2018.8602. Epub 2018 Feb 13.
Normal formation and function of the lungs are essential for the transition of the fetus to an air‑breathing environment at birth. The synthesis of pulmonary surfactant (PS), which is produced by type II alveolar epithelial cells (AECIIs), is required for proper lung development. Previous in vitro studies have suggested that PS synthesis is regulated by microRNA (miR)‑26a in fetal rat AECIIs. The present study explored the potential role of miR‑26a in lung development and PS synthesis by using a miR‑26a‑1/miR‑26a‑2 double knockout mouse model. Hematoxylin and eosin staining and transmission electron microscopy were used to observe the morphology of fetal lungs. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were performed to examine the mRNA and protein levels of surfactant‑associated proteins. The results demonstrated that the lung formation in the knockout mice was more mature, and that there were more mature lamellar bodies inside AECIIs in miR‑26a knockout mice at late stages of lung development. The findings further demonstrated that knockout of miR‑26a increased surfactant‑associated mRNA and protein expression levels. The results indicated that knockout of miR‑26a promotes lung development and PS synthesis.
正常的肺部形成和功能对于胎儿在出生时向空气呼吸环境的过渡至关重要。肺表面活性剂 (PS) 的合成是由 II 型肺泡上皮细胞 (AECII) 产生的，这对于正常的肺发育是必需的。先前的体外研究表明，PS 合成受胎鼠 AECII 中的 microRNA (miR) -26a 调节。本研究通过使用 miR-26a-1/miR-26a-2 双敲除小鼠模型探讨了 miR-26a 在肺发育和 PS 合成中的潜在作用。苏木精和伊红染色和透射电子显微镜用于观察胎肺的形态。逆转录-定量聚合酶链反应和 Western blot 分析用于检查与表面活性剂相关的蛋白的 mRNA 和蛋白水平。结果表明，敲除小鼠的肺形成更成熟，并且 miR-26a 敲除小鼠在肺发育晚期的 AECII 内有更多成熟的板层小体。这些发现进一步表明，miR-26a 的敲除增加了与表面活性剂相关的 mRNA 和蛋白表达水平。结果表明，miR-26a 的敲除促进了肺发育和 PS 的合成。
