Integrated Bioinformatic Analyses Reveal Immune Molecular Markers and Regulatory Networks for Cerebral Ischemia-Reperfusion
Background: Cerebral ischemia-reperfusion injury (CIR) following a stroke results in secondary damage and is a leading cause of adult disability. The present study aimed to identify hub genes and networks in CIR to explore potential therapeutic agents for its treatment. Methods: Differentially expre...
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IMR Press
2023-08-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/28/8/10.31083/j.fbl2808179 |
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| author | Qixin Guo Anning Du Jiayue Wang Luyang Wang Xu Zhu Xin Yue Shengen Liao Mengsha Shi Qiang Qu Iokfai Cheang Xinli Li Hui Pang Guoxin Tong |
| author_facet | Qixin Guo Anning Du Jiayue Wang Luyang Wang Xu Zhu Xin Yue Shengen Liao Mengsha Shi Qiang Qu Iokfai Cheang Xinli Li Hui Pang Guoxin Tong |
| author_sort | Qixin Guo |
| collection | DOAJ |
| description | Background: Cerebral ischemia-reperfusion injury (CIR) following a stroke results in secondary damage and is a leading cause of adult disability. The present study aimed to identify hub genes and networks in CIR to explore potential therapeutic agents for its treatment. Methods: Differentially expressed genes based on the GSE23163 dataset were identified, and weighted gene co-expression network analysis was performed to explore co-expression modules associated with CIR. Hub genes were identified by intersecting immune gene profiles, differentially expressed genes, and modular genes. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and transcription factor-microRNA-gene regulatory network analyses were then conducted in selected crucial modules. Subsequently, their expression levels in animal models were verified using real-time quantitative polymerase chain reaction and Western blotting. Finally, potential drug molecules were screened for, and molecular docking simulations were performed to identify potential therapeutic targets. Results: Seven hub genes—namely, Ccl3, Ccl4, Ccl7, Cxcl1, Hspa1a, Cd14, and Socs3—were identified. Furthermore, we established a protein interaction network using the STRING database and found that the core genes selected through the cytohubba plugin remained consistent. Animal experiments showed that at the transcriptional level, all seven genes showed significant differences (p < 0.001, fold change vs sham, 5–200). At the translational level, however, only Ccl3, Ccl4, Ccl7, Hspa1a, and Socs3 showed significant differences, while Cxcl1 and Cd14 did not. Nifedipine, with the highest predicted score, was identified as a therapeutic agent and successfully docked with the protein encoded by the hub genes. Conclusions: The expression of Ccl3, Ccl4, Ccl7, Hspa1a, and Socs3 was significantly different in CIR tissues compared to normal tissues both at the transcriptional and translational levels. Systems biology approaches indicated that these could be possible CIR marker genes, providing a stepping stone for further experimental studies. |
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| id | doaj.art-106c53f9f79b491dbf8ec8112ba0bcd6 |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-03-12T02:38:59Z |
| publishDate | 2023-08-01 |
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| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-106c53f9f79b491dbf8ec8112ba0bcd62023-09-04T09:13:41ZengIMR PressFrontiers in Bioscience-Landmark2768-67012023-08-0128817910.31083/j.fbl2808179S2768-6701(23)00817-1Integrated Bioinformatic Analyses Reveal Immune Molecular Markers and Regulatory Networks for Cerebral Ischemia-ReperfusionQixin Guo0Anning Du1Jiayue Wang2Luyang Wang3Xu Zhu4Xin Yue5Shengen Liao6Mengsha Shi7Qiang Qu8Iokfai Cheang9Xinli Li10Hui Pang11Guoxin Tong12Department of Cardiology, Affiliated Hangzhou First People's Hospital, Zhejiang University, School of Medicine, 310006 Hangzhou, Zhejiang, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, ChinaDepartment of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, Jiangsu, ChinaDepartment of Cardiology, Xuzhou Central Hospital, Xuzhou School of Clinical Medicine of Nanjing Medical University, 221009 Nanjing, Jiangsu, ChinaDepartment of Cardiology, Affiliated Hangzhou First People's Hospital, Zhejiang University, School of Medicine, 310006 Hangzhou, Zhejiang, ChinaBackground: Cerebral ischemia-reperfusion injury (CIR) following a stroke results in secondary damage and is a leading cause of adult disability. The present study aimed to identify hub genes and networks in CIR to explore potential therapeutic agents for its treatment. Methods: Differentially expressed genes based on the GSE23163 dataset were identified, and weighted gene co-expression network analysis was performed to explore co-expression modules associated with CIR. Hub genes were identified by intersecting immune gene profiles, differentially expressed genes, and modular genes. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and transcription factor-microRNA-gene regulatory network analyses were then conducted in selected crucial modules. Subsequently, their expression levels in animal models were verified using real-time quantitative polymerase chain reaction and Western blotting. Finally, potential drug molecules were screened for, and molecular docking simulations were performed to identify potential therapeutic targets. Results: Seven hub genes—namely, Ccl3, Ccl4, Ccl7, Cxcl1, Hspa1a, Cd14, and Socs3—were identified. Furthermore, we established a protein interaction network using the STRING database and found that the core genes selected through the cytohubba plugin remained consistent. Animal experiments showed that at the transcriptional level, all seven genes showed significant differences (p < 0.001, fold change vs sham, 5–200). At the translational level, however, only Ccl3, Ccl4, Ccl7, Hspa1a, and Socs3 showed significant differences, while Cxcl1 and Cd14 did not. Nifedipine, with the highest predicted score, was identified as a therapeutic agent and successfully docked with the protein encoded by the hub genes. Conclusions: The expression of Ccl3, Ccl4, Ccl7, Hspa1a, and Socs3 was significantly different in CIR tissues compared to normal tissues both at the transcriptional and translational levels. Systems biology approaches indicated that these could be possible CIR marker genes, providing a stepping stone for further experimental studies.https://www.imrpress.com/journal/FBL/28/8/10.31083/j.fbl2808179cerebral ischemia-reperfusiondifferentially expressed genehub genesischemic strokemolecular dockingnifedipineweighted gene co-expression network analysis |
| spellingShingle | Qixin Guo Anning Du Jiayue Wang Luyang Wang Xu Zhu Xin Yue Shengen Liao Mengsha Shi Qiang Qu Iokfai Cheang Xinli Li Hui Pang Guoxin Tong Integrated Bioinformatic Analyses Reveal Immune Molecular Markers and Regulatory Networks for Cerebral Ischemia-Reperfusion Frontiers in Bioscience-Landmark cerebral ischemia-reperfusion differentially expressed gene hub genes ischemic stroke molecular docking nifedipine weighted gene co-expression network analysis |
| title | Integrated Bioinformatic Analyses Reveal Immune Molecular Markers and Regulatory Networks for Cerebral Ischemia-Reperfusion |
| title_full | Integrated Bioinformatic Analyses Reveal Immune Molecular Markers and Regulatory Networks for Cerebral Ischemia-Reperfusion |
| title_fullStr | Integrated Bioinformatic Analyses Reveal Immune Molecular Markers and Regulatory Networks for Cerebral Ischemia-Reperfusion |
| title_full_unstemmed | Integrated Bioinformatic Analyses Reveal Immune Molecular Markers and Regulatory Networks for Cerebral Ischemia-Reperfusion |
| title_short | Integrated Bioinformatic Analyses Reveal Immune Molecular Markers and Regulatory Networks for Cerebral Ischemia-Reperfusion |
| title_sort | integrated bioinformatic analyses reveal immune molecular markers and regulatory networks for cerebral ischemia reperfusion |
| topic | cerebral ischemia-reperfusion differentially expressed gene hub genes ischemic stroke molecular docking nifedipine weighted gene co-expression network analysis |
| url | https://www.imrpress.com/journal/FBL/28/8/10.31083/j.fbl2808179 |
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