Hardie W D, Bruno M D, Huelsman K M, Iwamoto H S, Carrigan P E, Leikauf G D, Whitsett J A, Korfhagen T R
Department of Pediatrics, Children's Hospital Research Foundation, Cincinnati, Ohio, USA.
Am J Pathol. 1997 Oct;151(4):1075-83.
Developmental changes in lung morphology and physiology during postnatal alveolarization were assessed in transgenic mice expressing transforming growth factor-alpha (TGF-alpha) in pulmonary type II cells under control of the surfactant protein C gene promoter. TGF-alpha transcripts were identified in respiratory epithelial cells at 1 day of age to adulthood. Enlargement of alveolar airspaces and fibrosis were detected as early as 1 week of age, and the increased airspace progressed with advancing age. Specific lung compliance was significantly increased in lungs of transgenic mice by 2 weeks of age and was associated with airflow obstruction. Chronic expression of TGF-alpha in the lungs of newborn transgenic mice caused remodeling of the developing lung during the period of postnatal alveolarization, resulting in markedly enlarged parenchymal airspace, pulmonary fibrosis, and physiological abnormalities including airway obstruction and increased lung compliance.
在表面活性蛋白C基因启动子控制下，在肺II型细胞中表达转化生长因子-α（TGF-α）的转基因小鼠中，评估了出生后肺泡化过程中肺形态和生理学的发育变化。从1日龄到成年，在呼吸道上皮细胞中均鉴定出TGF-α转录本。早在1周龄时就检测到肺泡气腔增大和纤维化，并且随着年龄的增长，气腔增大加剧。到2周龄时，转基因小鼠肺的比顺应性显著增加，并伴有气流阻塞。新生转基因小鼠肺中TGF-α的持续表达导致出生后肺泡化期间发育中的肺发生重塑，导致实质气腔明显增大、肺纤维化以及包括气道阻塞和肺顺应性增加在内的生理异常。
