Rad1 attenuates DNA double-strand breaks and cell cycle arrest in type II alveolar epithelial cells of rats with bronchopulmonary dysplasia

Molecular Medicine

Research Article

Xindong Xue¹  Xin Tong¹  Xinyi Zhao¹  Wanjie Huang¹  Danni Li¹  Na Liu¹  Jianhua Fu¹  Dan Zhang¹ 

[1] Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China;

关键词: Bronchopulmonary dysplasia;    Arrested lung development;    DNA double-strand breaks;    Rad1;    Cell cycle arrest;   

DOI  :  10.1186/s10020-023-00660-3

 received in 2022-03-02, accepted in 2023-04-27,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundBronchopulmonary dysplasia (BPD) is the most common and serious chronic lung disease in preterm infants with pathological characteristics of arrested lung development. DNA double-strand breaks (DSBs) are a serious manifestation of oxidative stress damage, but little is known about the role of DSBs in BPD. The current study set out to detect DSB accumulation and cell cycle arrest in BPD and study the expression of genes related to DNA damage and repair in BPD through DNA damage signaling pathway-based PCR array to determine a suitable target to improve arrested lung development associated with BPD.MethodsDSB accumulation and cell cycle arrest were detected in a BPD animal model and primary cells, then a DNA damage signaling pathway-based PCR array was used to identify the target of DSB repair in BPD.ResultsDSB accumulation and cell cycle arrest were shown in BPD animal model, primary type II alveolar epithelial cells (AECII) and cultured cells after exposure to hyperoxia. Of the 84 genes in the DNA damage-signaling pathway PCR array, eight genes were overexpressed and 11 genes were repressed. Rad1, an important protein for DSB repair, was repressed in the model group. Real-time PCR and western blots were used to verify the microarray results. Next, we confirmed that silencing Rad1 expression aggravated the accumulation of DSBs and cell cycle arrest in AECII cells, whereas its overexpression alleviated DSB accumulation and cell cycle arrest.ConclusionsThe accumulation of DSBs in AECII might be an important cause of alveolar growth arrest associated with BPD. Rad1 could be an effective target for intervention to improve this arrest in lung development associated with BPD.

【 授权许可】

CC BY   
© The Author(s) 2023

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