Single-cell transcriptomes reveal heterogeneity of chlorine-induced mice acute lung injury and the inhibitory effect of pentoxifylline on ferroptosis
Abstract To investigate the effect of pentoxifylline (PTX) on Chlorine (Cl2)-induced acute lung injury (ALI) by single-cell RNA sequencing (scRNA-seq). Female BALB/c mice were exposed to Cl2 at 400 ppm for 15 min. H&E staining was used to observe the degree of lung injury. scRNA-seq was conducte...
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| Format: | Article |
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Nature Portfolio
2023-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-32093-7 |
| _version_ | 1797836513198735360 |
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| author | Chen-qian Zhao Chong Wang Meng-meng Liu Meng Cao Jie Peng De-qin Kong Xiao-ting Ren Rui Liu Chun-xu Hai Xiao-di Zhang |
| author_facet | Chen-qian Zhao Chong Wang Meng-meng Liu Meng Cao Jie Peng De-qin Kong Xiao-ting Ren Rui Liu Chun-xu Hai Xiao-di Zhang |
| author_sort | Chen-qian Zhao |
| collection | DOAJ |
| description | Abstract To investigate the effect of pentoxifylline (PTX) on Chlorine (Cl2)-induced acute lung injury (ALI) by single-cell RNA sequencing (scRNA-seq). Female BALB/c mice were exposed to Cl2 at 400 ppm for 15 min. H&E staining was used to observe the degree of lung injury. scRNA-seq was conducted to analysis of normal and Cl2-exposed mice lung tissues. Immunofluorescence was used to observe genes of interest. Thirty-two mice were randomly divided into four groups: Control, Cl2, Cl2+Fer-1, Cl2+PTX. TEM, WB and ELISA were used to detect ferroptosis-related indicators. The 5, 8, 10, 12, 16, 20 clusters were epithelial cells and 4, 15, 18, 19, 21 clusters were endothelial cells. Pseudo-time analysis revealed the differentiation trajectory of epithelial cells and key regulatory genes (Gclc, Bpifa1, Dnah5 and Dnah9) during the process of injury. Cell–cell communication analysis identified several important receptor–ligand complexes (Nrp1-Vegfa, Nrp2-Vegfa, Flt1-Vegfa and Flt4-Vegfa). Ferroptosis were found up-regulated in epithelial and endothelial cells by GSVA analysis. Highly expressed genes to which closely related ferroptosis were found by SCENIC analysis. PTX could significantly decrease the levels of MDA and abnormal high expression of solute carrier family 7 member 11 (SLC7A11, the key transporter of cystine) as well as increase the expression of GSH/GSSG and glutathione peroxidase 4 (GPX4) (p < 0.05). This study revealed novel molecular features of Cl2-induced ALI. PTX may be a potential specific drug by inhibiting the process of ferroptosis in epithelial and endothelial cells. |
| first_indexed | 2024-04-09T15:11:11Z |
| format | Article |
| id | doaj.art-e0abe0f8571f42b5939a89342a445999 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T15:11:11Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-e0abe0f8571f42b5939a89342a4459992023-04-30T11:14:25ZengNature PortfolioScientific Reports2045-23222023-04-0113111310.1038/s41598-023-32093-7Single-cell transcriptomes reveal heterogeneity of chlorine-induced mice acute lung injury and the inhibitory effect of pentoxifylline on ferroptosisChen-qian Zhao0Chong Wang1Meng-meng Liu2Meng Cao3Jie Peng4De-qin Kong5Xiao-ting Ren6Rui Liu7Chun-xu Hai8Xiao-di Zhang9Department of Medical Experiment Center, Shaanxi University of Chinese MedicineDepartment of Medical Experiment Center, Shaanxi University of Chinese MedicineDepartment of Health Service, Logistics University of Chinese People’s Armed Police ForceDepartment of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Medical UniversityDepartment of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Medical UniversityDepartment of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Medical UniversityDepartment of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Medical UniversityDepartment of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Medical UniversityDepartment of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Medical UniversityDepartment of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Medical UniversityAbstract To investigate the effect of pentoxifylline (PTX) on Chlorine (Cl2)-induced acute lung injury (ALI) by single-cell RNA sequencing (scRNA-seq). Female BALB/c mice were exposed to Cl2 at 400 ppm for 15 min. H&E staining was used to observe the degree of lung injury. scRNA-seq was conducted to analysis of normal and Cl2-exposed mice lung tissues. Immunofluorescence was used to observe genes of interest. Thirty-two mice were randomly divided into four groups: Control, Cl2, Cl2+Fer-1, Cl2+PTX. TEM, WB and ELISA were used to detect ferroptosis-related indicators. The 5, 8, 10, 12, 16, 20 clusters were epithelial cells and 4, 15, 18, 19, 21 clusters were endothelial cells. Pseudo-time analysis revealed the differentiation trajectory of epithelial cells and key regulatory genes (Gclc, Bpifa1, Dnah5 and Dnah9) during the process of injury. Cell–cell communication analysis identified several important receptor–ligand complexes (Nrp1-Vegfa, Nrp2-Vegfa, Flt1-Vegfa and Flt4-Vegfa). Ferroptosis were found up-regulated in epithelial and endothelial cells by GSVA analysis. Highly expressed genes to which closely related ferroptosis were found by SCENIC analysis. PTX could significantly decrease the levels of MDA and abnormal high expression of solute carrier family 7 member 11 (SLC7A11, the key transporter of cystine) as well as increase the expression of GSH/GSSG and glutathione peroxidase 4 (GPX4) (p < 0.05). This study revealed novel molecular features of Cl2-induced ALI. PTX may be a potential specific drug by inhibiting the process of ferroptosis in epithelial and endothelial cells.https://doi.org/10.1038/s41598-023-32093-7 |
| spellingShingle | Chen-qian Zhao Chong Wang Meng-meng Liu Meng Cao Jie Peng De-qin Kong Xiao-ting Ren Rui Liu Chun-xu Hai Xiao-di Zhang Single-cell transcriptomes reveal heterogeneity of chlorine-induced mice acute lung injury and the inhibitory effect of pentoxifylline on ferroptosis Scientific Reports |
| title | Single-cell transcriptomes reveal heterogeneity of chlorine-induced mice acute lung injury and the inhibitory effect of pentoxifylline on ferroptosis |
| title_full | Single-cell transcriptomes reveal heterogeneity of chlorine-induced mice acute lung injury and the inhibitory effect of pentoxifylline on ferroptosis |
| title_fullStr | Single-cell transcriptomes reveal heterogeneity of chlorine-induced mice acute lung injury and the inhibitory effect of pentoxifylline on ferroptosis |
| title_full_unstemmed | Single-cell transcriptomes reveal heterogeneity of chlorine-induced mice acute lung injury and the inhibitory effect of pentoxifylline on ferroptosis |
| title_short | Single-cell transcriptomes reveal heterogeneity of chlorine-induced mice acute lung injury and the inhibitory effect of pentoxifylline on ferroptosis |
| title_sort | single cell transcriptomes reveal heterogeneity of chlorine induced mice acute lung injury and the inhibitory effect of pentoxifylline on ferroptosis |
| url | https://doi.org/10.1038/s41598-023-32093-7 |
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