Table 2.
Specific molecular pathways implicated in liver I/R injury based on studies in mouse liver transplantation
| Molecule | Significance regarding I/R injury | Reference |
|---|---|---|
| Interferon regulatory factor-1 (IRF-1) |
IRF-1-deficient livers express neither death ligands nor death receptors and exhibit less cold I/R compared with WT livers |
Ueki S, Hepatology, 201038 |
| IRF-1 promotes liver transplant I/R injury via hepatocyte IL- 15/IL-15Ra production |
Yokota S, J Immunol 201539 | |
|
| ||
| T-cell activation gene-3 (TCA-3, CCL1) |
Neutralization by anti-TCA3 monoclonal antibody decreases neutrophil and T cell infiltration and attenuates cold I/R injury |
Xie JF Transplantation, 200637 |
|
| ||
| Toll-like receptor 4 (TLR4) | TLR4 KO liver grafts are protected from cold I/R injury | Shen XD, Liver Transpl, 200741 |
|
| ||
| JNK2 | JNK pathway induces mitochondrial depolarization and promotes hepatocyte death during cold I/R |
Theruvath TP, Am J Transpl, 200840 |
|
| ||
| B7 homolog1 (B7-H1) | Hepatocytes increase B7-H1 expression after cold I/R and induce T cell apoptosis in the graft |
Ueki S, Hepatology, 201145 |
|
| ||
| NTPDase-1 (CD39) | CD39 overexpression in liver grafts attenuates cold I/R injury | Pommery S, Hepatology, 201342 |
| CD39 deficiency exacerbates cold I/R. | Yoshida O, Hepatology, 201343 | |
|
| ||
| T cell immunoglobulin mucin- 1,3 (TIM-1,3) |
Anti-TIM-1 antibody treatment abolishes neutrophil/macrophage activation and reduces cold I/R injury |
Zhang Y, Am J Transplant, 201348 |
| TIM-3/Gal-9 activation protects livers from cold I/R injury | Liu Y, Am J Transplant, 201549 | |
|
| ||
| Type I interferon (IFN) | Type I IFN receptor (IFNAR) KO grafts that lack type I IFN signaling show less cold I/R injury compared with WT grafts. |
Shen XD, Am J Transplant, 201246 |
|
| ||
| Tumor necrosis factor-alpha (TNFα) |
Donor liver TNFR1 protects against cold I/R injury, whereas recipient TNFR1 promotes cold I/R injury |
Conzelmann LO, Transplantation, 200647 |