Hyperoxia exposure upregulates Dvl-1 and activates Wnt/β-catenin signaling pathway in newborn rat lung

BMC Molecular and Cell Biology

Research

Le Zhang¹  Yanyu Zhang¹  Yawen Li¹  Yuting Zhu¹  Zhengying Li¹  Weilai Jin¹  Yuanyuan Fang¹ 

[1] Department of Neonatology, The Affiliated Wuxi Children’s Hospital of Nanjing Medical University, No. 299-1 Qingyang Road, 214023, Wuxi, China;

关键词: Hyperoxia;    Lung injury;    Dvl-1;    Wnt/β-catenin;    Bronchopulmonary dysplasia;    Alveolar typeII epithelial cell;   

DOI  :  10.1186/s12860-023-00465-6

 received in 2022-09-29, accepted in 2023-01-30,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundBronchopulmonary dysplasia is a serious and lifelong pulmonary disease in premature neonates that influences around one-quarter of premature newborns. The wingless-related integration site /β-catenin signaling pathway, which is abnormally activated in the lungs with pulmonary fibrosis, affects cell differentiation and lung development.MethodsNewborn rats were subjected to hyperoxia exposure. Histopathological changes to the lungs were evaluated through immunohistochemistry, and the activation of disheveled and Wnt /β-catenin signaling pathway components was assessed by Western blotting and real-time PCR. The abilities of proliferation, apoptosis and migration were detected by Cell Counting Kit-8, flow cytometry and scratch wound assay, respectively.ResultsContrasting with normoxic lungs, hyperoxia-exposed lungs demonstrated larger alveoli, fewer alveoli and thicker alveolar septa. Superoxide dismutase activity was significantly decreased (7th day: P < 0.05; 14th day: P < 0.01) and malondialdehyde significantly increased (7th day: P < 0.05; 14th day: P < 0.01) after hyperoxia exposure. Protein and mRNA expression levels of β-catenin, Dvl-1, CTNNBL1 and cyclin D1 were significantly upregulated by hyperoxia exposure on 7th day (P < 0.01) and 14th day (P < 0.01). In hyperoxic conditions, Dvl-l downregulation and Dvl-l downregulation + MSAB treatment significantly increased the proliferation rates, decreased the apoptosis rates and improved the ability of cell migration. In hyperoxic conditions, Dvl-l downregulation could decrease the mRNA expression levels of GSK3β, β-catenin, CTNNBL1 and cyclin D1 and decrease the protein relative expression levels of GSK3β, p-GSK3β, β-catenin, CTNNBL1 and cyclin D1.ConclusionsWe confirmed the positive role of Dvl-1 and the Wnt/β-catenin signaling pathway in promoting BPD in hyperoxia conditions and provided a promising therapeutic target.

【 授权许可】

CC BY   
© The Author(s) 2023

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