title: Wnt5a reverses the inhibitory effect of hyperoxia on transdifferentiation of alveolar epithelial type II cells to type I cells.
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.
authors.affiliation: Department of Pediatrics, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, Liaoning, 110004, People's Republic of China. cmu2hxuwei@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Pediatrics, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, Liaoning, 110004, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pediatrics, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, Liaoning, 110004, People's Republic of China.
authors.forename: Ni
authors.initials: N
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, Liaoning, 110004, People's Republic of China.
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, Liaoning, 110004, People's Republic of China.
authors.forename: Guangfu
authors.initials: G
authors.lastname: Wen
authors.affiliation: Department of Pediatrics, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, Liaoning, 110004, People's Republic of China.
authors.forename: Binglun
authors.initials: B
authors.lastname: Zhang
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D049109:Cell Proliferation; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D005260:Female; D010100:Oxygen / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D051153:Wnt Proteins / Q000502:physiology*; D000071818:Wnt-5a Protein
chemical_list: D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C491837:Wnt5a protein, rat; D010100:Oxygen
keywords: AECIIs; AECIs; Hyperoxia; Preterm born; Wnt5a