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.