Abstract
Tumor necrosis factor receptor-associated factor (TRAF) proteins are a family of signaling molecules that function downstream of multiple receptor signaling pathways, and they play a pivotal role in the regulation of intracellular biological progresses. These TRAF-dependent signaling pathways and physiological functions have been involved in the occurrence and progression of ischemia-reperfusion injury (IRI), which is a common pathophysiological process that occurs in a wide variety of clinical events, including ischemic shock, organ transplantation, and thrombolytic therapy, resulting in a poor prognosis and high mortality. IRI occurs in multiple organs, including liver, kidney, heart, lung, brain, intestine, and retina. In recent years, mounting compelling evidence has confirmed that the genetic alterations of TRAFs can cause subversive phenotype changes during IRI of those organs. In this review, based on current knowledge, we summarized and analyzed the regulatory effect of TRAFs on the IRI of various organs, providing clear direction and a firm theoretical basis for the development of treatment strategies to manipulate TRAF proteins or TRAF-dependent signaling pathways in IRI-related diseases.
Highlights
We have proven the protective effects of TRAF2 in intestinal ischemia-reperfusion injury (IRI), which occurs in a wide variety of clinical conditions, including hemorrhagic shock, acute mesenteric ischemia, and organ transplantation, resulting in a high mortality rate that range from 70 to 80% (Higuchi et al, 2008; Jia et al, 2020)
IRI is a common pathological process which occurs frequently in ischemic stroke, surgical treatment such as resection and transplant, thromboembolic events, and various other clinic events requiring the restoration of blood supply after ischemia, causing serious damage to various organs and even tissues throughout the body, thereby leading to a poor prognosis and high mortality
Oxidative stress may promote the expression of pro-inflammatory regulatory factors, and inflammatory cells may induce the overproduction of reactive oxygen species (ROS), forming a vicious circle to promote the occurrence and development of various diseases, including IRI
Summary
Tumor necrosis factor receptor-associated factors (TRAFs) were identified as the signaling adaptors that positively and negatively regulate the signal transduction pathways of various receptors, including the TNF-R superfamily, Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), and cytokine receptors (Fang et al, 2017; Dhillon et al, 2019; Abbreviations: ALDOA, aldolase A; aPKC, atypical protein kinase C; ASK1, apoptosis signal-regulating kinase 1; AS-IV, Astragaloside IV; BBB, blood brain barrier; BMAL1, aryl hydrocarbon receptor nuclear translocator-like protein 1; CK, creatine kinase; CSFV, classical swine fever virus; EAD, early allograft dysfunction; ER, endoplasmic reticulum; EV71, enterovirus 71; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; hMSCs, human mesenchymal stem cells; HPV, human papilloma viruses; H/R, hypoxia/reoxygenation; IBD, inflammatory bowel disease; IFN-I, type I interferon; IPC, ischemic preconditioning; IPostC, ischemic postconditioning; IRI, ischemia-reperfusion injury; lncRNA, long non-coding RNA; LPS, lipopolysaccharide; LRIP, limb remote ischemic postconditioning; LV, left ventricular; MAPK, mitogen-activated protein kinase; Mbd2, methyl-CpG binding domain protein 2; miRNAs, microRNA; MLKL, mixed-lineage kinase domain-like; NAS, N-Acetylserotonin; NF-κB, nuclear factor-κB; NLR, NOD-like receptor; NLS, nuclear localization signal; OGDR, oxygenglucose deprivation reperfusion; ORF3a, open reading frame 3a; PI3K, phosphatidylinositol-3-kinase; PreD-SCP, preactivated and disaggregated shape-changed platelet; RLR, RIG-I-like receptor; SAB, salvianolic acid B; SARS-CoV, severe acute respiratory syndrome coronavirus; SLE, systemic lupus erythematosus; Sphk1, sphingosine kinase 1; TAK1, transforming growth factor-β-activated kinase 1; TGF-β, transforming growth factor-β; TLR, Toll-like receptor; TRAF, Tumor necrosis factor receptor-associated factor; TUDCA, tauroursodeoxycholic acid.Roles of TRAFs in IRISwaidani et al, 2019). Current research showed that TRAF1 played an important role in cerebral, liver, and myocardial IRI, and the TRAF1/ASK1 axis was the common signaling pathway involved in IRI regulation for these organs.
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