Novel Targets for Treating Ischemia-Reperfusion Injury in the Liver

Yang, Weili; Chen, Ji; Meng, Yuhuan; Chen, Zhenzhen; Yang, Jichun

doi:10.3390/ijms19051302

Cited by 62 publications

(76 citation statements)

References 103 publications

(140 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The following only covers a small picture of the novel modes of treatment against IRI in animal and clinical studies. This ranges from improvements in surgical techniques, targeting downstream targets of peroxisome proliferator-activated receptor-γ (PPAR-γ) in liver [40], to 'defatting' steatotic livers [41] and the use of gene therapies, such as RNA interference by siRNA [42]. He et al [43] presented a case report of an ischaemia-free liver transplantation (IFLT) surgical technique, involving the donation of a fatty liver.…”

Section: Novel Therapeutic Methods For Targeting Iri and Reconditionimentioning

confidence: 99%

“…In mice models, increase in PPAR-γ expression was shown to be protective against cell death. Identification of FAM3A, a target gene of PPAR-γ, was reported to elevate ATP levels and subsequent activation of the Akt signaling pathway, which inhibits apoptosis, mitigating IRI-related damages in liver cells [40].…”

Section: Novel Therapeutic Methods For Targeting Iri and Reconditionimentioning

confidence: 99%

See 1 more Smart Citation

The Effect of Preservation Temperature on Liver, Kidney, and Pancreas Tissue ATP in Animal and Preclinical Human Models

Bellini

Yiu

Nozdrin

et al. 2019

JCM

View full text Add to dashboard Cite

The recent advances in machine perfusion (MP) technology involve settings ranging between hypothermic, subnormothermic, and normothermic temperatures. Tissue level adenosine triphosphate (ATP) is a long-established marker of viability and functionality and is universal for all organs. In the midst of a growing number of complex clinical parameters for the quality assessment of graft prior to transplantation, a revisit of ATP may shed light on the underlying reconditioning mechanisms of different perfusion temperatures in the form of restoration of metabolic and energy status. This article aims to review and critically analyse animal and preclinical human studies (discarded grafts) during MP of three abdominal organs (liver, kidney, and pancreas) in which ATP was a primary endpoint. A selective review of recent novel reconditioning approaches relevant to mitigation of graft ischaemia-reperfusion injury via MP and for different perfusion temperatures was also conducted. With a current reiterated interest for oxygenation during MP, a re-introduction of tissue ATP levels may be valuable for graft viability assessment prior to transplantation. Further studies may help delineate the benefits of selective perfusion temperatures on organs viability.

show abstract

Section: Novel Therapeutic Methods For Targeting Iri and Reconditionimentioning

confidence: 99%

Section: Novel Therapeutic Methods For Targeting Iri and Reconditionimentioning

confidence: 99%

The Effect of Preservation Temperature on Liver, Kidney, and Pancreas Tissue ATP in Animal and Preclinical Human Models

Bellini

Yiu

Nozdrin

et al. 2019

JCM

View full text Add to dashboard Cite

show abstract

“…Although tremendous effort has been made in the past decades to decipher the underlying mechanisms of I/R injury, therapies that successfully translated into clinical practice remain scarce [1,2]. The present study depicts a previously unidenti ed role of miR-9-5p in the LSEC pathological processes using an in vitro I/R model.…”

Section: Discussionmentioning

confidence: 73%

“…Hepatic ischemia/reperfusion (I/R) injury, a major complication of liver surgeries, liver transplantation, and hemorrhagic shock, is attributable to deteriorated post-operational hepatic dysfunction, elongated hospital stay, as well as aggravated morbidity and mortality [1][2][3]. A crucial event during this process is the death of liver sinusoidal endothelial cells (LSECs), which takes place only a few minutes following reperfusion, several hours prior to detectable hepatocyte death [1,4].…”

Section: Introductionmentioning

confidence: 99%

Protective role of microRNA-9-5p in oxygen glucose deprivation/reperfusion-induced injury in liver sinusoidal endothelial cell

Duan¹,

Gao²,

Wang³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Maintenance of the function and survival of liver sinusoidal endothelial cells (LSECs) play a crucial role in hepatic ischemia/reperfusion (I/R) injury, a major cause of liver impairment during surgical treatment. Emerging evidence indicate a critical role of microRNAs in I/R injury. This study aims to investigate whether miR-9-5p exert a protective effect on LSECs in vitro .Methods: We transfected LSECs with miR-9-5p mimic or mimic NC. LSECs were treated with oxygen and glucose deprivation (OGD, 5% CO2 and 95% N2), followed by glucose-free DMEM medium for 6 h, and high-glucose (HG, 30 mmol/L glucose) DMEM medium for 12 h. The biological role of miR-9-5p in I/R-induced LSEC injury was determined. Results: In the in vitro model of OGD/HG injury in LSECs, the expression levels of miR-9-5p were significantly downregulated and those of CXC chemokine receptor-4 (CXCR4) upregulated. LSEC I/R injury led to deteriorated cell death, enhanced oxidative stress and excessive inflammatory response. Mechanistically, we showed that miR-9-5p overexpression significantly upregulated both mRNA and protein levels of CXCR4, followed by rescue of LSECs, ameliorated inflammatory response, and deactivation of pro-apoptotic signaling pathways.Conclusion: miR-9-5p promotes LSEC survival and inhibits apoptosis and inflammatory response in LSECs following OGD/HG injury via downregulation of CXCR4.

show abstract

“…The complicated IR injury is one of the main reasons for early graft failure and the increased risk of organ rejection and liver dysfunction [3]. Unfortunately, currently, the promising interventions for the treatment of hepatic IR injury are limited in number [4][5][6]. Thus, more effective strategies that can reduce hepatic IR injury and improve graft viability are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

Mild Hypothermia Attenuates Hepatic Ischemia–Reperfusion Injury through Regulating the JAK2/STAT3-CPT1a-Dependent Fatty Acid β-Oxidation

Wang

Xia

et al. 2020

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Hepatic ischemia–reperfusion (IR) injury is a clinical issue that can result in poor outcome and lacks effective therapies at present. Mild hypothermia (32–35°C) is a physiotherapy that has been reported to significantly alleviate IR injury, while its protective effects are attributed to multiple mechanisms, one of which may be the regulation of fatty acid β-oxidation (FAO). The aim of the present study was to investigate the role and underlying mechanisms of FAO in the protective effects of mild hypothermia. We used male mice to establish the experimental models as previously described. In brief, before exposure to in situ ischemia for 1 h and reperfusion for 6 h, mice received pretreatment with mild hypothermia for 2 h and etomoxir (inhibitor of FAO) or leptin (activator of FAO) for 1 h, respectively. Then, tissue and blood samples were collected to evaluate the liver injury, oxidative stress, and changes in hepatic FAO. We found that mild hypothermia significantly reduced the hepatic enzyme levels and the score of hepatic pathological injury, hepatocyte apoptosis, oxidative stress, and mitochondrial injury. In addition, the expression of the rate-limiting enzyme (CPT1a) of hepatic FAO was downregulated almost twofold by IR, while this inhibition could be significantly reversed by mild hypothermia. Experiments with leptin and etomoxir confirmed that activation of FAO could also reduce the hepatic enzyme levels and the score of hepatic pathological injury, hepatocyte apoptosis, oxidative stress, and mitochondrial injury induced by IR, which had the similar effects to mild hypothermia, while inhibition of FAO had negative effects. Furthermore, mild hypothermia and leptin could promote the phosphorylation of JAK2/STAT3 and upregulate the ratio of BCL-2/BAX to suppress hepatocyte apoptosis. Thus, we concluded that FAO played an important role in hepatic IR injury and mild hypothermia attenuated hepatic IR injury mainly via the regulation of JAK2/STAT3-CPT1a-dependent FAO.

show abstract

Novel Targets for Treating Ischemia-Reperfusion Injury in the Liver

Cited by 62 publications

References 103 publications

The Effect of Preservation Temperature on Liver, Kidney, and Pancreas Tissue ATP in Animal and Preclinical Human Models

The Effect of Preservation Temperature on Liver, Kidney, and Pancreas Tissue ATP in Animal and Preclinical Human Models

Protective role of microRNA-9-5p in oxygen glucose deprivation/reperfusion-induced injury in liver sinusoidal endothelial cell

Mild Hypothermia Attenuates Hepatic Ischemia–Reperfusion Injury through Regulating the JAK2/STAT3-CPT1a-Dependent Fatty Acid β-Oxidation

Contact Info

Product

Resources

About