Identifying nexilin as a central gene in neutrophil-driven abdominal aortic aneurysm pathogenesis
Abstract Objectives Abdominal aortic aneurysm (AAA) is an inflammation-driven disease in which neutrophil infiltration is critical to its progression. This study aims to explore the molecular mechanisms behind neutrophil infiltration in AAA and identify key regulatory genes. Methods We utilized weig...
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| Format: | Article |
| Language: | English |
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BMC
2025-03-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-025-01157-x |
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| author | Bohan Yang Yiyan Xu Fengfei Yan Cheng Peng Ye Song Song Han Haiyang Wang |
| author_facet | Bohan Yang Yiyan Xu Fengfei Yan Cheng Peng Ye Song Song Han Haiyang Wang |
| author_sort | Bohan Yang |
| collection | DOAJ |
| description | Abstract Objectives Abdominal aortic aneurysm (AAA) is an inflammation-driven disease in which neutrophil infiltration is critical to its progression. This study aims to explore the molecular mechanisms behind neutrophil infiltration in AAA and identify key regulatory genes. Methods We utilized weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis to compare AAA and healthy abdominal aortic tissues. Functional enrichment analysis and a protein–protein interaction (PPI) network were constructed to understand gene functions. Machine learning algorithms were applied to identify key hub genes, followed by in vivo validation using an ApoE-/- mouse model. Results Neutrophils, NK cells, and pDCs were significantly increased in AAA tissues. WGCNA identified 234 genes associated with neutrophil infiltration, of which 39 were significantly differentially expressed. Functional enrichment analysis highlighted roles in actin-related processes and pathways. Nexilin (NEXN) was consistently identified as a key hub gene negatively correlated with immune cell infiltration. In vivo validation confirmed that NEXN inhibits AAA progression in ApoE-/- mice by regulating immune cell infiltration. Conclusion NEXN plays a crucial role in modulating neutrophil infiltration in AAA. These findings provide new molecular insights into AAA pathogenesis and suggest NEXN as a potential target for AAA therapy. |
| format | Article |
| id | doaj-art-d4971cd667e34adfa3f0bd8e433d190a |
| institution | DOAJ |
| issn | 1528-3658 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-d4971cd667e34adfa3f0bd8e433d190a2025-08-20T02:49:35ZengBMCMolecular Medicine1528-36582025-03-0131112110.1186/s10020-025-01157-xIdentifying nexilin as a central gene in neutrophil-driven abdominal aortic aneurysm pathogenesisBohan Yang0Yiyan Xu1Fengfei Yan2Cheng Peng3Ye Song4Song Han5Haiyang Wang6Department of Vascular Surgery, The First Affiliated Hospital of Guangzhou Medical UniversityDepartment of Vascular Surgery, The First Affiliated Hospital of Guangzhou Medical UniversityDepartment of Vascular Surgery, The First Affiliated Hospital of Guangzhou Medical UniversityDepartment of Vascular Surgery, The First Affiliated Hospital of Guangzhou Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Vascular Surgery, The First Affiliated Hospital of Guangzhou Medical UniversityDepartment of Vascular Surgery, The First Affiliated Hospital of Guangzhou Medical UniversityAbstract Objectives Abdominal aortic aneurysm (AAA) is an inflammation-driven disease in which neutrophil infiltration is critical to its progression. This study aims to explore the molecular mechanisms behind neutrophil infiltration in AAA and identify key regulatory genes. Methods We utilized weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis to compare AAA and healthy abdominal aortic tissues. Functional enrichment analysis and a protein–protein interaction (PPI) network were constructed to understand gene functions. Machine learning algorithms were applied to identify key hub genes, followed by in vivo validation using an ApoE-/- mouse model. Results Neutrophils, NK cells, and pDCs were significantly increased in AAA tissues. WGCNA identified 234 genes associated with neutrophil infiltration, of which 39 were significantly differentially expressed. Functional enrichment analysis highlighted roles in actin-related processes and pathways. Nexilin (NEXN) was consistently identified as a key hub gene negatively correlated with immune cell infiltration. In vivo validation confirmed that NEXN inhibits AAA progression in ApoE-/- mice by regulating immune cell infiltration. Conclusion NEXN plays a crucial role in modulating neutrophil infiltration in AAA. These findings provide new molecular insights into AAA pathogenesis and suggest NEXN as a potential target for AAA therapy.https://doi.org/10.1186/s10020-025-01157-xAbdominal aortic aneurysmNeutrophilsWeighted gene co-expression network analysisNexilinImmune cell infiltrationMachine learning |
| spellingShingle | Bohan Yang Yiyan Xu Fengfei Yan Cheng Peng Ye Song Song Han Haiyang Wang Identifying nexilin as a central gene in neutrophil-driven abdominal aortic aneurysm pathogenesis Molecular Medicine Abdominal aortic aneurysm Neutrophils Weighted gene co-expression network analysis Nexilin Immune cell infiltration Machine learning |
| title | Identifying nexilin as a central gene in neutrophil-driven abdominal aortic aneurysm pathogenesis |
| title_full | Identifying nexilin as a central gene in neutrophil-driven abdominal aortic aneurysm pathogenesis |
| title_fullStr | Identifying nexilin as a central gene in neutrophil-driven abdominal aortic aneurysm pathogenesis |
| title_full_unstemmed | Identifying nexilin as a central gene in neutrophil-driven abdominal aortic aneurysm pathogenesis |
| title_short | Identifying nexilin as a central gene in neutrophil-driven abdominal aortic aneurysm pathogenesis |
| title_sort | identifying nexilin as a central gene in neutrophil driven abdominal aortic aneurysm pathogenesis |
| topic | Abdominal aortic aneurysm Neutrophils Weighted gene co-expression network analysis Nexilin Immune cell infiltration Machine learning |
| url | https://doi.org/10.1186/s10020-025-01157-x |
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