Hyperoxia stimulates the transdifferentiation of type II alveolar epithelial cells in newborn rats

被引:60
作者
Hou, Ana [1 ]
Fu, Jianhua [1 ]
Yang, Haiping [1 ]
Zhu, Yuting [1 ]
Pan, Yuqing [1 ]
Xu, Shuyan [1 ]
Xue, Xindong [1 ]
机构
[1] China Med Univ, Shengjing Hosp, Dept Pediat, Shenyang 110004, Peoples R China
关键词
transdifferentiation; alveolar epithelial cells; hyperoxia; bronchopulmonary dysplasia; KERATINOCYTE GROWTH-FACTOR; CHRONIC LUNG-DISEASE; BRONCHOPULMONARY DYSPLASIA; PREMATURE RATS; NEONATAL-RATS; MOUSE MODEL; EXPRESSION; SURFACTANT; EXPOSURE; OXYGEN;
D O I
10.1152/ajplung.00099.2014
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Supplemental oxygen treatment in preterm infants may cause bronchopulmonary dysplasia (BPD), which is characterized by alveolar simplification and vascular disorganization. Despite type II alveolar epithelial cell (AEC II) damage being reported previously, we found no decrease in the AEC II-specific marker, surfactant protein C (SP-C), in the BPD model in our previous study. We thus speculated that AEC II injury is not a unique mechanism of BPD-related pulmonary epithelial repair dysfunction and that abnormal transdifferentiation can exist. Newborn rats were randomly assigned to model (85% oxygen inhalation) and control groups (room air inhalation). Expressions of AEC I (aquaporin 5, T1 alpha) and AEC II markers (SP-C, SP-B) were detected at three levels: 1) in intact lung tissue, 2) in AEC II isolated from rats in the two groups, and 3) in AEC II isolated from newborn rats, which were further cultured under either hyperoxic or normoxic conditions. In the model group, increased AEC I was observed at both the tissue and cell level, and markedly increased transdifferentiation was observed by immunofluorescent double staining. Transmission electron microscopy revealed morphological changes in alveolar epithelium such as damaged AECs, a fused air-blood barrier structure, and opened tight junctions in the model group. These findings indicate that transdifferentiation of AECs is not suppressed but rather is increased under hyperoxic treatment by compensation; however, such repair during injury cannot offset pulmonary epithelial air exchange and barrier dysfunction caused by structural damage to AECs.
引用
收藏
页码:L861 / L872
页数:12
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