Wnt3a Mediates the Inhibitory Effect of Hyperoxia on the Transdifferentiation of AECIIs to AECIs
Wnt3a Mediates the Inhibitory Effect of Hyperoxia on the Transdifferentiation of AECIIs to AECIs
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DOI：
10.1369/0022155415600032
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发表时间：
2015-07
影响因子：
3.2
通讯作者：
W. Xu;Ying Zhao;Binglun Zhang;Bo Xu;Yang Yang-Yang;Yujing Wang;Chunfeng Liu
中科院分区：
文献类型：
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作者：
W. Xu;Ying Zhao;Binglun Zhang;Bo Xu;Yang Yang-Yang;Yujing Wang;Chunfeng Liu
本研究旨在探讨Wnt 3a在高氧条件下II型肺泡上皮细胞（AECIIs）向I型肺泡上皮细胞（AECIs）转分化中的作用。在体内研究中，早产大鼠暴露于高氧21天。在体外研究中，原代大鼠AECIIs进行高氧和常氧暴露交替每24小时7天。利用siRNA介导的Wnt 3a敲除和外源性Wnt 3a研究Wnt 3a对AECIIs向AECIs转分化的影响。Wnt 5a过表达的AECII也用于研究Wnt 3a是否可以抵消Wnt 5a的作用。结果表明，高氧可导致早产大鼠肺泡损伤，Wnt 3a表达增加，β-catenin在细胞核内聚集。此外，在高氧暴露后，Wnt 3a/β-catenin信号在分离的AECII中被激活。Wnt 3a基因敲除可阻断高氧对转分化的抑制作用，而Wnt 3a基因的加入则加剧了这种抑制作用。此外，Wnt 3a的加入阻断了Wnt 5a在高氧暴露的Wnt 5a过表达的AECII中的转分化促进作用。总之，我们的结果表明，激活的Wnt 3a/β-catenin信号可能参与了高氧诱导的AECIIs向AECIs转分化的抑制。
The aim of this study is to investigate the effect of Wnt3a in the transdifferentiation of type II alveolar epithelial cells (AECIIs) to type I alveolar epithelial cells (AECIs) under hyperoxia condition. In the in vivo study, preterm rats were exposed in hyperoxia for 21 days. In the in vitro study, primary rat AECIIs were subjected to a hyperoxia and normoxia exposure alternatively every 24 hr for 7 days. siRNA-mediated knockout of Wnt3a and exogenous Wnt3a were used to investigate the effect of Wnt3a on transdifferentiation of AECIIs to AECIs. Wnt5a-overexpressed AECIIs were also used to investigate whether Wnt3a could counteract the effect of Wnt5a. The results showed that hyperoxia induced alveolar damage in the lung of preterm born rats, as well as an increased expression of Wnt3a and nuclear accumulation of β-catenin. In addition, Wnt3a/β-catenin signaling was activated in isolated AECIIs after hyperoxia exposure. Wnt3a knockout blocked the inhibition of the transdifferentiation induced by hyperoxia, and Wnt3a addition exacerbated this inhibition. Furthermore, Wnt3a addition blocked the transdifferentiation-promoting effect of Wnt5a in hyperoxia-exposed Wnt5a-overexpressed AECIIs. In conclusion, our results demonstrate that the activated Wnt3a/β-catenin signal may be involved in the hyperoxia-induced inhibition of AECIIs’ transdifferentiation to AECIs.