USP4 deficiency exacerbates hepatic ischaemia/reperfusion injury via TAK1 signalling

Zhou, Jiangqiao; Qiu, Tao; Wang, Tianyu; Chen, Zhongbao; Ma, Xiaofen; Zhang, Long; Zou, Jilin

doi:10.1042/cs20180959

Cited by 16 publications

(17 citation statements)

References 35 publications

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“…As TLR-4-NF-κB pathway in KCs is a classical signalling pathway and is activated during liver IRI, which is the main reason for sterile inflammation and hepatocellular apoptosis [38], we also detected the impact of IL-4 on these in vivo and in vitro. IL-4 treatment suppressed the inflammatory response and cell apoptosis induced by IRI and LPS.…”

Section: Discussionmentioning

confidence: 95%

IL‐4 Alleviates Ischaemia‐Reperfusion Injury by Inducing Kupffer Cells M2 Polarization via STAT6‐JMJD3 Pathway after Rat Liver Transplantation

Deng

Wang

et al. 2020

BioMed Research International

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Background. Liver ischaemia-reperfusion injury (IRI) remains a problem in liver transplantation. Interleukin-4 (IL-4) has been found to reduce liver IRI, but the exact mechanism remains unclear. Methods. Donor livers were infused with recombinant IL-4 or normal saline during cold storage, and the hepatocellular apoptosis and the inflammatory response were detected. The effect of IL-4 treatment on Kupffer cells (KCs) polarization and expression of the STAT6-JMJD3 pathway was evaluated in vivo and in vitro. KCs in donor livers were depleted by clodronate liposome treatment or JMJD3 was inhibited by GSK-J4 before liver transplantation to determine whether the protective effect of IL-4 treatment was dependent on KCs. Results. IL-4 treatment decreased sALT and sAST levels and alleviated hepatocellular apoptosis and inflammation at 6 h after liver transplantation. IL-4 treatment induced KCs alternatively activated (M2) polarization in vitro and in vivo, and the expression of STAT6 and JMJD3 was increased. JMJD3 knockdown abolished KCs M2 polarization and reduced the antiapoptotic and anti-inflammatory effects induced by IL-4 treatment in vitro. In addition, the protection of IL-4 treatment against IRI induced by liver transplantation was significantly reduced after the depletion of KCs or the inhibition of JMJD3 in donor livers. Conclusions. IL-4 treatment-induced KCs M2 polarization was dependent on the STAT6-JMJD3 pathway and protected liver grafts from IRI after liver transplantation.

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Section: Discussionmentioning

confidence: 95%

IL‐4 Alleviates Ischaemia‐Reperfusion Injury by Inducing Kupffer Cells M2 Polarization via STAT6‐JMJD3 Pathway after Rat Liver Transplantation

Deng

Wang

et al. 2020

BioMed Research International

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“…In addition, USP4 was reported to block inflammatory responses induced by TLR− NF-κB and IL-1R− NF-κB signaling pathways by targeting TRAF6 and TAK1 [35,36]. USP4 knockout mice displayed enhancement of TAK1-NF-κB mediated liver inflammation in a hepatic ischaemia/reperfusion model [54]. Consistent with these findings, we found that USP4 knockdown in lung cancer cells increased phosphorylation of RelA, which is essential for NF-κB activation, and enhanced both basal and stimulus-induced inflammatory cytokine production, including production evoked by TNF-α and TLR ligands.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Silencing of Ubiquitin Specific Protease 4 by Snail1 Contributes to Macrophage-Dependent Inflammation and Therapeutic Resistance in Lung Cancer

Lai

Yeh

et al. 2020

Cancers

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There is a positive feedback loop driving tumorigenesis and tumor growth through coordinated regulation of epigenetics, inflammation, and stemness. Nevertheless, the molecular mechanism linking these processes is not well understood. In this study, we analyzed the correlation of de-ubiquitinases (DUBs) expression with survival data from the OncoLnc database. Among the DUBs analyzed, ubiquitin specific protease 4 (USP4) had the lowest negative Cox coefficient. Low expression of USP4 was associated with poor survival among lung cancer patients and was inversely correlated with expression of stemness and inflammation markers. Expression of USP4 were reduced at more advanced stages of lung cancer. Mechanistically, expression of USP4 was downregulated in snail1-overexpressing and stemness-enriched lung cancer cells. Snail1 was induced in lung cancer cells by interaction with macrophages, and epigenetically suppressed USP4 expression by promoter methylation. Stable knockdown of USP4 in lung cancer cells enhanced inflammatory responses, stemness properties, chemotherapy resistance, and the expression of molecules allowing escape from immunosurveillance. Further, mice injected with USP4 knockdown lung cancer cells demonstrated enhanced tumorigenesis and tumor growth. These results reveal that the Snail1-mediated suppression of USP4 is a potential mechanism to orchestrate epigenetic regulation, inflammation and stemness for macrophage-promoted tumor progression.

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“…The mouse hepatic I/R injury model was constructed according to the classical method with some small modifications ( 4 , 14 , 15 ). Mice underwent fasting for 12 h before surgery and were given free access to drinking water.…”

Section: Methodsmentioning

confidence: 99%

Ubiquitin-Specific Peptidase 10 Protects Against Hepatic Ischaemic/Reperfusion Injury via TAK1 Signalling

et al. 2020

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Ubiquitin-specific peptidase 10 (USP10) protein is a deubiquitination enzyme involved in many important biological processes. However, the function of USP10 in hepatic ischaemic/reperfusion (I/R) injury remains unknown. The aim of this study was to explore the role of USP10 in hepatic I/R injury. USP10 Heterozygote mice and primary hepatocytes were used to construct hepatic I/R models. The effect of USP10 on hepatic I/R injury was examined via pathological and molecular analyses. Our results indicated that USP10 was significantly downregulated in the livers of mice after hepatic I/R injury and in hepatocytes subjected to hypoxia/reoxygenation stimulation. USP10 Heterozygote mice exhibited exacerbated hepatic I/R injury, as evidenced by enhanced liver inflammation via the NF-κB signalling pathway and increased hepatocyte apoptosis. Additionally, USP10 overexpression inhibited hepatocyte inflammation and apoptosis in hepatic I/R injury in vitro and in vivo . Mechanistically, our study demonstrated that USP10 knockdown exerted its detrimental effects on hepatic I/R injury by inducing activation of the transforming growth factor β-activated kinase 1 (TAK1)-JNK/p38 signalling pathways. TAK1 was required for USP10 function in hepatic I/R injury as TAK1 inhibition abolished USP10 function in vitro . In conclusion, our study demonstrated that USP10 plays a protective role in hepatic I/R injury by inhibiting the activation of the TAK1-JNK/p38 signalling pathways. Modulation of USP10/TAK1 might be a promising strategy to prevent this pathological process.

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USP4 deficiency exacerbates hepatic ischaemia/reperfusion injury via TAK1 signalling

Cited by 16 publications

References 35 publications

IL‐4 Alleviates Ischaemia‐Reperfusion Injury by Inducing Kupffer Cells M2 Polarization via STAT6‐JMJD3 Pathway after Rat Liver Transplantation

IL‐4 Alleviates Ischaemia‐Reperfusion Injury by Inducing Kupffer Cells M2 Polarization via STAT6‐JMJD3 Pathway after Rat Liver Transplantation

Epigenetic Silencing of Ubiquitin Specific Protease 4 by Snail1 Contributes to Macrophage-Dependent Inflammation and Therapeutic Resistance in Lung Cancer

Ubiquitin-Specific Peptidase 10 Protects Against Hepatic Ischaemic/Reperfusion Injury via TAK1 Signalling

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