King L S, Nielsen S, Agre P
Department of Medicine, Division of Pulmonary and Critical Care Medicine, John Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
J Clin Invest. 1996 May 15;97(10):2183-91. doi: 10.1172/JCI118659.
At birth water is rapidly reabsorbed from the distal lung in preparation for alveolar gas exchange. To investigate a potential role for the AQP1 water channel in development, lung membranes from fetal and perinatal rats were analyzed by immunoblot. First expression of AQP1 was noted in fetal rat lung at E19 (19th day of the 21-day gestation). The level of AQP1 increased fivefold from the last gestational day to the first postnatal day and persisted at high levels into adulthood. Maternal corticosteroids increased expression of AQP1 in fetal lung, an effect also seen in adult rats. AQP1 mRNA increased in rat pups treated with corticosteroids, suggesting at least partial regulation at the level of transcription. Immunohistochemical analyses with anti-AQP1 demonstrated the protein in peribronchial vessels and visceral pleura at E21 with increased postnatal expression. AQP1 was not expressed in airway epithelium, and only occasional alveolar pneumocytes were labeled. Immunoelectron microscopy revealed AQP1 on both apical and basolateral membranes of endothelial cells. The ontogeny and corticosteroid induction of AQP1 in rat lung coincide with major physiological alterations in lung development; however, the distribution of AQP1 predicts the existence of other water channels in the alveolar epithelium.
出生时,水分迅速从肺远端被重吸收,为肺泡气体交换做准备。为研究水通道蛋白1(AQP1)水通道在发育过程中的潜在作用,采用免疫印迹法分析了胎鼠和围生期大鼠的肺膜。首先在胚胎第19天(21天妊娠期的第19天)的胎鼠肺中检测到AQP1的表达。从妊娠最后一天到出生后第一天,AQP1的水平增加了五倍,并在成年期持续维持在高水平。母体皮质类固醇增加了胎鼠肺中AQP1的表达,在成年大鼠中也观察到了这种效应。用皮质类固醇处理的幼鼠中AQP1 mRNA增加,提示至少在转录水平存在部分调控。用抗AQP1进行免疫组织化学分析显示,在胚胎第21天,支气管周围血管和脏层胸膜中有该蛋白,出生后表达增加。AQP1在气道上皮中不表达,仅偶尔有肺泡上皮细胞被标记。免疫电子显微镜显示,AQP1在内皮细胞的顶端和基底外侧膜上均有表达。大鼠肺中AQP1的个体发生和皮质类固醇诱导与肺发育中的主要生理变化一致;然而,AQP1的分布预示着肺泡上皮中存在其他水通道。