ArticleTransplant immunology2014
Protective role of bortezomib in steatotic liver ischemia/reperfusion injury through abrogation of MMP activation and YKL-40 expression.
Article in Transplant immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 34 citations in OpenAlex.
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- Inflammatory Effects and Regulatory Mechanisms of Chitinase-3-like-1 in Multiple Human Body Systems: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Inflammatory setting, therapeutic strategies targeting some pro-inflammatory cytokines and pathways in mitigating ischemia/reperfusion-induced hepatic injury: a comprehensive review.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Uncovering novel mechanisms of chitinase-3-like protein 1 in driving inflammation-associated cancers.Cancer cell international · 2024Review
- Myocardial interaction of apixaban after experimental acute volume overload.The Journal of international medical research · 2022Article
- Bortezomib Inhibits Lung Fibrosis and Fibroblast Activation without Proteasome Inhibition.American journal of respiratory cell and molecular biology · 2022Article
- Early reversibility of histological changes after experimental acute cardiac volume-overload.American journal of cardiovascular disease · 2022Article
- Chitinase-3 like-protein-1 function and its role in diseases.Signal transduction and targeted therapy · 2020Review
- Alterations of IL-1 and VEGF After Ischemia-Reperfusion Injured Uterus and Ovary in Rats.Medeniyet medical journal · 2020Article
- Genome-Wide RNAi Screen Identifies Regulators of Cardiomyocyte Necrosis.ACS pharmacology & translational science · 2019Article
- Nobiletin ameliorates hepatic ischemia and reperfusion injury through the activation of SIRT-1/FOXO3a-mediated autophagy and mitochondrial biogenesis.Experimental & molecular medicine · 2019Article
- Hepatoprotective Effects ofOxidative medicine and cellular longevity · 2019Article
- Protective Role of mTOR in Liver Ischemia/Reperfusion Injury: Involvement of Inflammation and Autophagy.Oxidative medicine and cellular longevity · 2019Review
- Monoamine oxidase A inhibition protects the myocardium after experimental acute volume overload.Anatolian journal of cardiology · 2019Article
- Proteasome and Organs Ischemia-Reperfusion Injury.International journal of molecular sciences · 2017Review
- Surgical Acute Volume-Overload Impacts Early on Myocardium - An Experimental Study.Acta Cardiologica Sinica · 2017Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Steatotic liver grafts tolerate ischemia-reperfusion (I/R) injury poorly, contributing to poor survival following transplantation. However the molecular mechanisms leading to I/R injury still remain to be defined. We have previously reported that the protective effect of bortezomib towards inhibiting cold induced I/R injury in obese rat liver transplant model is through NF-κB down modulation. In this report using an orthotopic liver transplant (OLT) model in Zucker rats (from obese, leptin deficient donor, to lean recipient) we defined the mechanisms of steatotic liver injury, and characterized the role of bortezomib in inhibiting MMP activation and YKL-40, both of which are involved in extracellular matrix deposition and fibrosis, the key pathological features of liver allograft failure. Obese donor rats were treated with bortezomib (i.v., 0.1mg/kg immediately prior to liver procurement) to assess the role of MMP and YKL-40 in steatotic liver I/R injury. I/R injury in steatotic livers resulted in significant increases in expression of YKL-40 (9 fold), and activation of MMP-2 (15 fold)/MMP-9 (12 fold). Bortezomib treatment reduced the expression of YKL-40 and MMP to basal levels. Bortezomib also inhibited the pro-fibrotic (VEGF, HGF, bFGF, TGF-β) and pro-inflammatory (IL-1β, TNF-α and IFN-γ) cytokines significantly in comparison to untreated animals with I/R injury. These results demonstrate that I/R injury in steatotic livers following transplantation are associated with MMP activation and YKL-40 upregulation resulting in pro-fibrotic and pro-inflammatory cytokine release. Administration of the proteosomal inhibitor, bortezomib, effectively attenuated the I/R injury by inhibiting MMP and YKL-40 expression and therefore support the clinical utility of this drug in donor management for preventing I/R injury and its sequelae.
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