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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Chen, Jing Lu, Tu Chen, Chen Zheng, Wenbin Lu, Lin Li, Naiyang |
| Abstract | Background Age-related macular degeneration (AMD), is a neurodegenerative ocular disease. This study investigated the role of ferroptosis-related genes and their interaction with immune cell infiltration in AMD. Methods We screened differential expression genes (DEGs) of AMD from data sets in Gene Expression Omnibus. We identified ferroptosis-related differentially expressed genes (ferroDEGs) by intersecting DEGs with ferroptosis-related genes. Protein–protein interactions network and Cytoscape were used for screening hub genes. Next, we analyzed immune cell infiltration using CIBERSORT and examined the crosstalk between hub ferroDEGs and immune cell infiltration. Hub genes expression in each cell cluster and the proportions of different cell clusters between AMD and normal samples were examined using single-cell data. The hub ferroDEG expressions were verified in cell and mouse models using RT–qPCR, western blot, and immunofluorescence assay. The roles of ANXA1 in ferroptosis and its crosstalk with microglia were investigated. Results We identified hub ferroDEGs that include six genes (ANXA1, DKK1, CD44, VIM, TGFB2, DUSP1). Functional analysis of those hub ferroDEGs was found to be correlated with leukocyte migration and chemotaxis, macrophage migration, and gliogenesis. The high-risk ferroptosis group exhibited elevated levels of CD8+ T cells, activated NK cells, and M2 macrophages. Single-cell sequencing data revealed a high degree of cell heterogeneity in macular degeneration and the monocytes proportion in the macular area was higher in AMD samples. Moreover, we observed elevated mRNA and protein levels of CD44, ANXA1 (P < 0.01), while ANXA1 knockdown reduced GPX4 expression in the cell model. Finally, we validated increased ANXA1 expression and observed its colocalization with microglia in mouse models using immunofluorescence assays. Conclusions This study offers insights into the AMD pathogenesis and identifies ANXA1 as a potential target related to protecting from ferroptosis and immune response for future research. Graphical Abstract |
| Related Links | https://eurjmedres.biomedcentral.com/counter/pdf/10.1186/s40001-024-02163-1.pdf |
| Ending Page | 24 |
| Page Count | 24 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| DOI | 10.1186/s40001-024-02163-1 |
| Journal | European Journal of Medical Research |
| Issue Number | 1 |
| Volume Number | 29 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2024-12-23 |
| Access Restriction | Open |
| Subject Keyword | Medicine Public Health Infectious Diseases Internal Medicine Surgery Oncology Biomedicine Age-related macular degeneration Ferroptosis Immune cell infiltration ANXA1 Medicine/Public Health |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine |
| Journal Impact Factor | 2.8/2023 |
| 5-Year Journal Impact Factor | 2.9/2023 |
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