Rad1 attenuates DNA double-strand breaks and cell cycle arrest in type II alveolar epithelial cells of rats with bronchopulmonary dysplasia
Abstract Background Bronchopulmonary 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 abou...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-023-00660-3 |
| _version_ | 1797817932814745600 |
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| author | Xin Tong Danni Li Na Liu Wanjie Huang Xinyi Zhao Dan Zhang Xindong Xue Jianhua Fu |
| author_facet | Xin Tong Danni Li Na Liu Wanjie Huang Xinyi Zhao Dan Zhang Xindong Xue Jianhua Fu |
| author_sort | Xin Tong |
| collection | DOAJ |
| description | Abstract Background Bronchopulmonary 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. Methods DSB 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. Results DSB 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. Conclusions The 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. |
| first_indexed | 2024-03-13T09:00:40Z |
| format | Article |
| id | doaj.art-9a004fda73e141169b247b90e5a13502 |
| institution | Directory Open Access Journal |
| issn | 1528-3658 |
| language | English |
| last_indexed | 2024-03-13T09:00:40Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj.art-9a004fda73e141169b247b90e5a135022023-05-28T11:19:43ZengBMCMolecular Medicine1528-36582023-05-0129111410.1186/s10020-023-00660-3Rad1 attenuates DNA double-strand breaks and cell cycle arrest in type II alveolar epithelial cells of rats with bronchopulmonary dysplasiaXin Tong0Danni Li1Na Liu2Wanjie Huang3Xinyi Zhao4Dan Zhang5Xindong Xue6Jianhua Fu7Department of Pediatrics, Shengjing Hospital of China Medical UniversityDepartment of Pediatrics, Shengjing Hospital of China Medical UniversityDepartment of Pediatrics, Shengjing Hospital of China Medical UniversityDepartment of Pediatrics, Shengjing Hospital of China Medical UniversityDepartment of Pediatrics, Shengjing Hospital of China Medical UniversityDepartment of Pediatrics, Shengjing Hospital of China Medical UniversityDepartment of Pediatrics, Shengjing Hospital of China Medical UniversityDepartment of Pediatrics, Shengjing Hospital of China Medical UniversityAbstract Background Bronchopulmonary 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. Methods DSB 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. Results DSB 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. Conclusions The 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.https://doi.org/10.1186/s10020-023-00660-3Bronchopulmonary dysplasiaArrested lung developmentDNA double-strand breaksRad1Cell cycle arrest |
| spellingShingle | Xin Tong Danni Li Na Liu Wanjie Huang Xinyi Zhao Dan Zhang Xindong Xue Jianhua Fu Rad1 attenuates DNA double-strand breaks and cell cycle arrest in type II alveolar epithelial cells of rats with bronchopulmonary dysplasia Molecular Medicine Bronchopulmonary dysplasia Arrested lung development DNA double-strand breaks Rad1 Cell cycle arrest |
| title | Rad1 attenuates DNA double-strand breaks and cell cycle arrest in type II alveolar epithelial cells of rats with bronchopulmonary dysplasia |
| title_full | Rad1 attenuates DNA double-strand breaks and cell cycle arrest in type II alveolar epithelial cells of rats with bronchopulmonary dysplasia |
| title_fullStr | Rad1 attenuates DNA double-strand breaks and cell cycle arrest in type II alveolar epithelial cells of rats with bronchopulmonary dysplasia |
| title_full_unstemmed | Rad1 attenuates DNA double-strand breaks and cell cycle arrest in type II alveolar epithelial cells of rats with bronchopulmonary dysplasia |
| title_short | Rad1 attenuates DNA double-strand breaks and cell cycle arrest in type II alveolar epithelial cells of rats with bronchopulmonary dysplasia |
| title_sort | rad1 attenuates dna double strand breaks and cell cycle arrest in type ii alveolar epithelial cells of rats with bronchopulmonary dysplasia |
| topic | Bronchopulmonary dysplasia Arrested lung development DNA double-strand breaks Rad1 Cell cycle arrest |
| url | https://doi.org/10.1186/s10020-023-00660-3 |
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