FPR1 affects acute rejection in kidney transplantation by regulating iron metabolism in neutrophils
Abstract Background Acute rejection (AR) is one of the significant factors contributing to poor prognosis in patients following kidney transplantation. Neutrophils are the main cause of early host-induced tissue injury. This paper intends to investigate the possible mechanisms of neutrophil involvem...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-025-01077-w |
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| author | Peiyuan Li Wenbin Ji Baotong Zhang Haowen Jia Jinmiao Wang Zhaonan Sun Yifan Wang Weiwei Wang Feng Qi |
| author_facet | Peiyuan Li Wenbin Ji Baotong Zhang Haowen Jia Jinmiao Wang Zhaonan Sun Yifan Wang Weiwei Wang Feng Qi |
| author_sort | Peiyuan Li |
| collection | DOAJ |
| description | Abstract Background Acute rejection (AR) is one of the significant factors contributing to poor prognosis in patients following kidney transplantation. Neutrophils are the main cause of early host-induced tissue injury. This paper intends to investigate the possible mechanisms of neutrophil involvement in acute rejection in renal transplantation. Methods Samples were analyzed for their relationship with immune cells using CIBERSORT. WGCNA was used to identify modules with high relevance to neutrophils and hub genes in the modules were extracted. The effect on neutrophil function after blocking formyl peptide receptor 1 (FPR1) was tested in vitro experiments. The effects of blocking FPR1 on neutrophil function as well as acute rejection were tested in vivo after constructing a mouse kidney transplant model. Results The proportion of neutrophils was higher in the AR group than in the non-rejection group, and FPR1 was identified as an important gene in the regulation of acute rejection in kidney transplantation by neutrophils. At the cellular level, blocking FPR1 inhibited the activation of the ERK1/2 pathway, decreased ferrous ion content, affected the expression of iron metabolism-related proteins, and suppressed the formation of NETs. In the acute rejection model of renal transplantation, blockade of FPR1 decreased graft neutrophil infiltration and NETs content. Meanwhile, blocking FPR1 attenuated graft injury during acute rejection. Conclusion This study found that FPR1 might be an important molecule involved in neutrophils during acute rejection of kidney transplantation, explored the relationship between kidney transplantation and neutrophils, and provided potential treatment methods for clinical practice. |
| format | Article |
| id | doaj-art-e63a693fa80a4111826fd97ca3652145 |
| institution | Kabale University |
| issn | 1528-3658 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-e63a693fa80a4111826fd97ca36521452025-01-26T12:38:42ZengBMCMolecular Medicine1528-36582025-01-0131112010.1186/s10020-025-01077-wFPR1 affects acute rejection in kidney transplantation by regulating iron metabolism in neutrophilsPeiyuan Li0Wenbin Ji1Baotong Zhang2Haowen Jia3Jinmiao Wang4Zhaonan Sun5Yifan Wang6Weiwei Wang7Feng Qi8Department of General Surgery, Tianjin Medical University General HospitalDepartment of General Surgery, Tianjin Medical University General HospitalDepartment of General Surgery, Tianjin Medical University General HospitalDepartment of General Surgery, Tianjin Medical University General Hospital Airport HospitalDepartment of Breast and Thyroid Surgery, Tianjin Union Medical Center, Nankai UniversityDepartment of General Surgery, Tianjin Medical University General HospitalDepartment of General Surgery, Tianjin Medical University General HospitalDepartment of General Surgery, Tianjin Baodi Hospital, Tianjin Medical University Baodi HospitalDepartment of General Surgery, Tianjin Medical University General HospitalAbstract Background Acute rejection (AR) is one of the significant factors contributing to poor prognosis in patients following kidney transplantation. Neutrophils are the main cause of early host-induced tissue injury. This paper intends to investigate the possible mechanisms of neutrophil involvement in acute rejection in renal transplantation. Methods Samples were analyzed for their relationship with immune cells using CIBERSORT. WGCNA was used to identify modules with high relevance to neutrophils and hub genes in the modules were extracted. The effect on neutrophil function after blocking formyl peptide receptor 1 (FPR1) was tested in vitro experiments. The effects of blocking FPR1 on neutrophil function as well as acute rejection were tested in vivo after constructing a mouse kidney transplant model. Results The proportion of neutrophils was higher in the AR group than in the non-rejection group, and FPR1 was identified as an important gene in the regulation of acute rejection in kidney transplantation by neutrophils. At the cellular level, blocking FPR1 inhibited the activation of the ERK1/2 pathway, decreased ferrous ion content, affected the expression of iron metabolism-related proteins, and suppressed the formation of NETs. In the acute rejection model of renal transplantation, blockade of FPR1 decreased graft neutrophil infiltration and NETs content. Meanwhile, blocking FPR1 attenuated graft injury during acute rejection. Conclusion This study found that FPR1 might be an important molecule involved in neutrophils during acute rejection of kidney transplantation, explored the relationship between kidney transplantation and neutrophils, and provided potential treatment methods for clinical practice.https://doi.org/10.1186/s10020-025-01077-wAcute rejectionKidney transplantationFPR1NeutrophilIron metabolism |
| spellingShingle | Peiyuan Li Wenbin Ji Baotong Zhang Haowen Jia Jinmiao Wang Zhaonan Sun Yifan Wang Weiwei Wang Feng Qi FPR1 affects acute rejection in kidney transplantation by regulating iron metabolism in neutrophils Molecular Medicine Acute rejection Kidney transplantation FPR1 Neutrophil Iron metabolism |
| title | FPR1 affects acute rejection in kidney transplantation by regulating iron metabolism in neutrophils |
| title_full | FPR1 affects acute rejection in kidney transplantation by regulating iron metabolism in neutrophils |
| title_fullStr | FPR1 affects acute rejection in kidney transplantation by regulating iron metabolism in neutrophils |
| title_full_unstemmed | FPR1 affects acute rejection in kidney transplantation by regulating iron metabolism in neutrophils |
| title_short | FPR1 affects acute rejection in kidney transplantation by regulating iron metabolism in neutrophils |
| title_sort | fpr1 affects acute rejection in kidney transplantation by regulating iron metabolism in neutrophils |
| topic | Acute rejection Kidney transplantation FPR1 Neutrophil Iron metabolism |
| url | https://doi.org/10.1186/s10020-025-01077-w |
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