| Targeting TRAF3 signaling protects against hepatic ischemia/reperfusions injury | |
| Hu J.; Zhu X.-H.; Zhang X.-J.; Wang P.-X.; Zhang R.; Zhang P.; Zhao G.-N.; Gao L.; Zhang X.-F.; Tian S.; Li H. | |
| 2016 | |
| Source Publication | Journal of Hepatology
 |
| ISSN | 1688278 |
| Volume | 64Issue:1Pages:146 |
| Abstract | Background & Aims The hallmarks of hepatic ischemia/reperfusion (I/R) injury, a common clinical problem that occurs during liver surgical procedures, include severe cell death and inflammatory responses that contribute to early graft failure and a higher incidence of organ rejection. Unfortunately, effective therapeutic strategies are limited. Tumor necrosis factor receptor (TNFR)-associated factor (TRAF) 3 transduces apoptosis and/or inflammation-related signaling pathways to regulate cell survival and cytokine production. However, the role of TRAF3 in hepatic I/R-induced liver damage remains unknown. Methods Hepatocyte- or myeloid cell-specific TRAF3 knockdown or transgenic mice were subjected to an I/R model in vivo, and in vitro experiments were performed by treating primary hepatocytes from these mice with hypoxia/reoxygenation stimulation. The function of TRAF3 in I/R-induced liver damage and the potential underlying mechanisms were investigated through various phenotypic analyses and biological approaches. Results Hepatocyte-specific, but not myeloid cell-specific, TRAF3 deficiency reduced cell death, inflammatory cell infiltration, and cytokine production in both in vivo and in vitro hepatic I/R models, whereas hepatic TRAF3 overexpression resulted in the opposite effects. Mechanistically, TRAF3 directly binds to TAK1, which enhances the activation of the downstream NF-κB and JNK pathways. Importantly, inhibition of TAK1 almost completely reversed the TRAF3 overexpression-mediated exacerbation of I/R injury. Conclusions TRAF3 is a novel hepatic I/R mediator that promotes liver damage and inflammation via TAK1-dependent activation of the JNK and NF-κB pathways. Inhibition of hepatic TRAF3 may represent a promising approach to protect the liver against I/R injury-related diseases. © 2015 European Association for the Study of the Liver. |
| Keyword | Cell death Hepatic ischemia/reperfusion Inflammation TAK1 TRAF3 |
| DOI | 10.1016/j.jhep.2015.08.021 |
| URL | View the original |
| Language | 英语 |
| The Source to Article | Scopus |
| Fulltext Access | |
| Citation statistics | |
| Document Type | Journal article |
| Collection | University of Macau |
| Recommended Citation GB/T 7714 | Hu J.,Zhu X.-H.,Zhang X.-J.,et al. Targeting TRAF3 signaling protects against hepatic ischemia/reperfusions injury[J]. Journal of Hepatology,2016,64(1):146. |
| APA | Hu J..,Zhu X.-H..,Zhang X.-J..,Wang P.-X..,Zhang R..,...&Li H..(2016).Targeting TRAF3 signaling protects against hepatic ischemia/reperfusions injury.Journal of Hepatology,64(1),146. |
| MLA | Hu J.,et al."Targeting TRAF3 signaling protects against hepatic ischemia/reperfusions injury".Journal of Hepatology 64.1(2016):146. |
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