PMID- 38266883
OWN - NLM
STAT- MEDLINE
DCOM- 20240314
LR  - 20240314
IS  - 1878-5492 (Electronic)
IS  - 0966-3274 (Linking)
VI  - 83
DP  - 2024 Apr
TI  - Exploration of the shared gene signatures and biological mechanisms between 
      ischemia-reperfusion injury and antibody-mediated rejection in renal 
      transplantation.
PG  - 102001
LID - S0966-3274(24)00017-0 [pii]
LID - 10.1016/j.trim.2024.102001 [doi]
AB  - BACKGROUND: Antibody-mediated rejection (ABMR) plays a crucial role in graft loss 
      during allogeneic renal transplantation. In renal transplantation, 
      ischemia-reperfusion injury (IRI) is unavoidable, serves as a major contributor 
      to acute rejection, and is linked to graft loss. However, the mechanisms 
      underlying IRI and ABMR are unclear. Therefore, this study aimed to investigate 
      the shared genetic characteristics and biological mechanisms between IRI and 
      ABMR. METHODS: Gene expressions for IRI (GSE43974) and ABMR (GSE129166 and 
      GSE36059) were retrieved from the Gene Expression Omnibus database. The shared 
      differentially expressed genes (DEGs) of IRI and ABMR were identified, and 
      subsequent functional enrichment analysis was performed. Immune cell infiltration 
      in ABMR and its relationship with the shared DEGs were investigated using the 
      CIBERSORT method. Random forest analysis, a protein-protein interaction network, 
      and Cytoscape were used to screen hub genes, which were subsequently subjected to 
      gene set enrichment analysis, miRNA prediction, and transcription factors 
      analysis. The survival analysis was performed through Kaplan-Meier curves. 
      Finally, drug compound prediction was performed on the shared DEGs using the Drug 
      Signature Database. RESULTS: Overall, 27 shared DEGs were identified between the 
      renal IRI and ABMR groups. Among these, 24 genes exhibited increased 
      co-expression, whereas none showed decreased co-expression. The shared DEGs were 
      primarily enriched in the inflammation signaling pathways. Notably, CD4 memory T 
      cells were identified as potential critical mediators of IRI, leading to ABMR. 
      Tumor necrosis factor alpha-induced protein 3 (TNFAIP3), interferon regulatory 
      factor 1 (IRF1), and early growth response 2 (EGR2) were identified as key 
      components in the potential mechanism that link IRI and ABMR. Patients undergoing 
      renal transplantation with higher expression levels of TNFAIP3, IRF1, and EGR2 
      exhibited decreased survival rates compared to those with lower expression 
      levels. CONCLUSION: Inflammation is a key mechanism that links IRI and ABMR, with 
      a potential role played by CD4 memory T cells. Furthermore, TNFAIP3, IRF1, and 
      EGR2 are implicated in the underlying mechanism between IRI and ABMR.
CI  - Copyright (c) 2024 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Jiang, Shan
AU  - Jiang S
AD  - Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Su, Hua
AU  - Su H
AD  - Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China. Electronic address: 
      dr_suhua@hust.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20240122
PL  - Netherlands
TA  - Transpl Immunol
JT  - Transplant immunology
JID - 9309923
RN  - 0 (Antibodies)
SB  - IM
MH  - Humans
MH  - *Kidney Transplantation
MH  - Kidney/pathology
MH  - Antibodies/metabolism
MH  - *Reperfusion Injury/metabolism
MH  - Inflammation/metabolism
OTO - NOTNLM
OT  - Antibody-mediated rejection
OT  - Bioinformatics
OT  - Hub genes
OT  - Ischemia-reperfusion injury
OT  - Renal transplantation
COIS- Declaration of competing interest The authors declare that the research was 
      conducted in the absence of any commercial or financial relationships that could 
      be construed as a potential conflict of interest.
EDAT- 2024/01/25 00:42
MHDA- 2024/03/14 06:47
CRDT- 2024/01/24 19:17
PHST- 2023/06/17 00:00 [received]
PHST- 2023/12/22 00:00 [revised]
PHST- 2024/01/20 00:00 [accepted]
PHST- 2024/03/14 06:47 [medline]
PHST- 2024/01/25 00:42 [pubmed]
PHST- 2024/01/24 19:17 [entrez]
AID - S0966-3274(24)00017-0 [pii]
AID - 10.1016/j.trim.2024.102001 [doi]
PST - ppublish
SO  - Transpl Immunol. 2024 Apr;83:102001. doi: 10.1016/j.trim.2024.102001. Epub 2024 
      Jan 22.