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Wnt5a reverses the inhibitory effect of hyperoxia on transdifferentiation of alveolar epithelial type II cells to type I cells

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Abstract

Transdifferentiation of alveolar epithelial type II cells (AECIIs) to type I cells (AECIs) is critical for reestablishment and maintenance of an intact alveolar epithelium. However, this process is frequently destroyed by hyperoxia treatment, which is commonly used in respiratory distress syndrome therapy in preterm infants. Wnt5a is considered to participate in this physiopathologic process, but the clear mechanisms still need to be further investigated. In this study, preterm rats and primary rat AECIIs were exposed to hyperoxia. Hematoxylin and eosin staining was used to examine the histological changes of the lungs. Real-time PCR and western blotting were used to examine Wnt5a expression and biomarkers of AECII and AECI expression. Immunohistochemistry and immunofluorescence were also used to determine the expression and location of selected biomarkers. Furthermore, AECIIs transfected with Wnt5a gene and exogenous Wnt5a were used to examine whether Wnt5a contributes to the transdifferentiation of AECIIs to AECIs. Results showed that hyperoxia inhibited the transdifferentiation of AECIIs to AECIs in vitro, which is represented by biomarkers of two types of cell that remained unchanged. In addition, Wnt5a protein expression was found to be decreased after hyperoxia exposure in vitro and in vivo. Furthermore, both the overexpression of Wnt5a and exogenous Wnt5a addition blocked the inhibitory effect of hyperoxia in vitro. In conclusion, our results suggest that the transdifferentiation of AECIIs to AECIs is impaired by hyperoxia, and this process may be associated with Wnt5a downregulation. Targeting Wnt5a may have the potential for the therapy of lung injury in preterm infants induced by hyperoxia.

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Acknowledgments

This work was supported by a grant from the National Natural Science Foundation of China (No. 81270726).

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Authors and Affiliations

  1. Department of Pediatrics, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, Liaoning, 110004, People’s Republic of China

    Wei Xu, Ying Zhao, Ni Yang, Chunfeng Liu, Guangfu Wen & Binglun Zhang

  2. Department of Ophthalmology, The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, People’s Republic of China

    Bo Xu

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  1. Wei Xu
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  2. Bo Xu
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  7. Binglun Zhang
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Correspondence to Wei Xu.

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The experiment was designed by Wei Xu. The manuscript was written by Wei Xu and Bo Xu. The experiment was performed by Bo Xu, Ying Zhao, Ni Yang, Chunfeng Liu, Guangfu Wen, and Binglun Zhang. The data were analyzed by Wei Xu and Bo Xu.

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Xu, W., Xu, B., Zhao, Y. et al. Wnt5a reverses the inhibitory effect of hyperoxia on transdifferentiation of alveolar epithelial type II cells to type I cells. J Physiol Biochem 71, 823–838 (2015). https://doi.org/10.1007/s13105-015-0446-4

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  • DOI: https://doi.org/10.1007/s13105-015-0446-4

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