Interferon Regulatory Factor 1 Activates Autophagy to Aggravate Hepatic Ischemia-Reperfusion Injury by Increasing High Mobility Group Box 1 Release

Z, Cui; Li, Shipeng; Liu, Zirong; Zhang, Yamin; Zhang, Haiming

doi:10.1159/000491732

Cited by 23 publications

(19 citation statements)

References 30 publications

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“…Of particular relevance to the present investigation is the report that levels of IRF‐1 increase within the liver after IR exposure 12 . Moreover, IRF‐1 knockout, which reduces the expression and release of high mobility group protein (HMGB1), relieves liver IRI 13 …”

Section: Introductionmentioning

confidence: 72%

Autophagic activation of IRF‐1 aggravates hepatic ischemia–reperfusion injury via JNK signaling

et al. 2021

MedComm

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Increasing evidence has accrued indicating that autophagy is associated with hepatic ischemia–reperfusion injury (IRI). This report demonstrates that interferon regulatory factor‐1 (IRF‐1) was upregulated in response to hepatic IRI and was associated with autophagic activation. As a result of these processes, there is an aggravation of liver damage, effects that can be offset by IRF‐1 depletion. In addition, these effects of IRF‐1 are associated with JNK pathway activation followed by increases in Beclin1 protein levels. This JNK‐induced autophagic cell death then leads to cell failure, and plays an important role in liver function damage. We conclude that IRF‐1 activates autophagy through JNK‐mediated autophagy. Accordingly, these findings indicating that the IRF‐1/JNK pathway activates autophagy to exacerbate liver IRI in this mouse model may provide new insights into novel protective therapies for hepatic IRI.

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Section: Introductionmentioning

confidence: 72%

Autophagic activation of IRF‐1 aggravates hepatic ischemia–reperfusion injury via JNK signaling

et al. 2021

MedComm

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“…These results were similar with the previous reports showing IRF-1 played an important role in ischemic neuronal death in mice or dead ischemic patients [ 15 ]. IRF-1 was also reported to aggravate hepatic ischemic/reperfusion injury [ 42 ]. Our results also showed that activating LXRs inhibited the expression of IRF-1 on transcription level, which was in agreement with previous reports showing that LXR ligands inhibit neither STAT1 phosphorylation nor STAT1 translocation to the nucleus but rather inhibit STAT1 binding to the promoters and the expression of IRF-1 [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

T0901317, an Agonist of Liver X Receptors, Attenuates Neuronal Apoptosis in Early Brain Injury after Subarachnoid Hemorrhage in Rats via Liver X Receptors/Interferon Regulatory Factor/P53 Upregulated Modulator of Apoptosis/Dynamin‐1‐Like Protein Pathway

Dai

Okada

et al. 2021

Oxidative Medicine and Cellular Longevity

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Background and Purpose. T0901317, a liver X receptor (LXR) agonist, is widely used to explore the functions of LXRs. T0901317 exerts antiapoptotic effects in many central nervous system disease models. Our aim was to detect the role of T0901317 in neuronal apoptosis in early brain injury after subarachnoid hemorrhage. Methods. Subarachnoid hemorrhage (SAH) models of Sprague-Dawley rats were established with perforation method. T0901317 was injected intraperitoneally 1-hour post-SAH. GSK2033, an inhibitor of LXRs, and interferon regulatory factor (IRF-1) CRISPR activation were injected intracerebroventricularly to evaluate potential signaling pathway. The severity of SAH, neurobehavior test in both short- and long-term and apoptosis was measured with Western blot and immunofluorescence staining. Results. Expression of LXR-α and IRF-1 increased and peaked at 24 h post-SAH, while LXR-β remained unaffected in SAH+vehicle group compared with Sham group. Post-SAH T0901317 treatment attenuated neuronal impairments in both short- and long-term and decreased neuronal apoptosis, the expression of IRF-1, P53 upregulated modulator of apoptosis (PUMA), dynamin-1-like protein (Drp1), Bcl-2-associated X protein (Bax) and cleaved caspase-3, and increasing B-cell lymphoma 2 (Bcl-2) at 24 h from modeling. GSK2033 inhibited LXRs and reversed T0901317’s neuroprotective effects. IRF-1 CRISPR activation upregulated the expression of IRF-1 and abolished the treatment effects of T0901317. Conclusion. T0901317 attenuated neuronal apoptosis via LXRs/IRF-1/PUMA/Drp1 pathway in SAH rats.

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“…IRF-1 plays a harmful role in liver IR [ 12 , 13 ], as well as reperfusion injury in other organs [ 12 , 14 , 15 ]. More recently, IRF-1 KO mice studies have shown that inhibiting autophagy was protective in hepatic IR [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Interferon Regulatory Factor-1 (IRF1) activates autophagy to promote liver ischemia/reperfusion injury by inhibiting β-catenin in mice

et al. 2020

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Autophagy is an important factor in liver ischemia-reperfusion injury. In the current study we investigate the function of interferon regulatory factor-1 (IRF1) in regulating autophagy to promote hepatic ischemia reperfusion injury (IR). The high expression of IRF1 during hepatic IR exhibited increased liver damage and was associated with activation of autophagy shown by Western blot markers, as well as immunofluorescent staining for autophagosomes. These effects were diminished by IRF1 deficiency in IRF1 knock out (KO) mice. Moreover, the autophagy inhibitor 3-MA decreased IR-induced liver necrosis and markedly abrogated the rise in liver injury tests (AST/ALT). β-catenin expression decreased during liver IR and was increased in the IRF1 KO mice. Immunoprecipitation assay showed the binding between IRF1 and β-catenin. Overexpression of IRF1 induced autophagy and also inhibited the expression of β-catenin. β-catenin inhibitor increased autophagy while β-catenin agonist suppressed autophagy in primary mouse hepatocytes. These results indicate that IRF1 induced autophagy aggravates hepatic IR injury in part by inhibiting β-catenin and suggests that targeting IRF1 may be an effective strategy in reducing hepatic IR injury.

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Interferon Regulatory Factor 1 Activates Autophagy to Aggravate Hepatic Ischemia-Reperfusion Injury by Increasing High Mobility Group Box 1 Release

Cited by 23 publications

References 30 publications

Autophagic activation of IRF‐1 aggravates hepatic ischemia–reperfusion injury via JNK signaling

Autophagic activation of IRF‐1 aggravates hepatic ischemia–reperfusion injury via JNK signaling

T0901317, an Agonist of Liver X Receptors, Attenuates Neuronal Apoptosis in Early Brain Injury after Subarachnoid Hemorrhage in Rats via Liver X Receptors/Interferon Regulatory Factor/P53 Upregulated Modulator of Apoptosis/Dynamin‐1‐Like Protein Pathway

Interferon Regulatory Factor-1 (IRF1) activates autophagy to promote liver ischemia/reperfusion injury by inhibiting β-catenin in mice

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