ArticleJournal of hepatology2014
MMP-9 deficiency shelters endothelial PECAM-1 expression and enhances regeneration of steatotic livers after ischemia and reperfusion injury.
Article in Journal of hepatology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 61 citations in OpenAlex.
- MMP-9 and non-invasive markers in evaluating MASLD and atherosclerosis.Journal, genetic engineering & biotechnology · 2026Article
- Eosinophil-derived apoptotic extracellular vesicles accelerate steatotic liver repair after ischemia/reperfusion injury through mitochondria-associated metabolic reprogramming.Journal of nanobiotechnology · 2026Article
- Topical frankincense treatment on relieving high-risk diabetic foot in rats by reducing inflammation and improving microcirculation.Frontiers in pharmacology · 2025Article
- Oncoprotein SET-associated transcription factor ZBTB11 triggers lung cancer metastasis.Nature communications · 2024Article
- A Multidrug Donor Preconditioning Improves Steatotic Rat Liver Allograft Function and Recipient Survival After Transplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2024Article
- Effect of Percutaneous Biliary Drainage on Enzyme Activity of Serum Matrix Metalloproteinase-9 in Patients with Malignant Hilar Obstructive Hyperbilirubinemia.Medicina (Kaunas, Lithuania) · 2023Article
- Piperine as Therapeutic Agent in Paracetamol-Induced Hepatotoxicity in Mice.Pharmaceutics · 2022Article
- Article
- Protective effect of ischemic postconditioning on ischemia reperfusion injury in steatotic rat livers.Annals of translational medicine · 2021Article
- Rg3-enriched Korean Red Ginseng extract inhibits blood-brain barrier disruption in an animal model of multiple sclerosis by modulating expression of NADPH oxidase 2 and 4.Journal of ginseng research · 2021Article
- Minimizing Ischemia Reperfusion Injury in Xenotransplantation.Frontiers in immunology · 2021Review
- The Protective Effect ofFrontiers in pharmacology · 2021Article
- Retinal Physiology and Circulation: Effect of Diabetes.Comprehensive Physiology · 2020Review
- Matrix Metalloproteinases as Potential Biomarkers and Therapeutic Targets in Liver Diseases.Cells · 2020Review
- Acute changes in the retina and central retinal artery with methamphetamine.Experimental eye research · 2020Article
- Interactions between neutrophil extracellular traps and activated platelets enhance procoagulant activity in acute stroke patients with ICA occlusion.EBioMedicine · 2020Article
- The Inhibition of Aldose Reductase Accelerates Liver Regeneration through Regulating Energy Metabolism.Oxidative medicine and cellular longevity · 2020Article
- Loss of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) in the Diabetic Retina: Role of Matrix Metalloproteinases.Investigative ophthalmology & visual science · 2019Article
- Overproduction of Tenascin-C Driven by Lipid Accumulation in the Liver Aggravates Hepatic Ischemia/Reperfusion Injury in Steatotic Mice.Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society · 2019Article
- Oleic Acid Protects against Hepatic Ischemia and Reperfusion Injury in Mice by Inhibiting AKT/mTOR Pathways.Oxidative medicine and cellular longevity · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsOrgan shortage has led to the use of steatotic livers in transplantation, despite their elevated susceptibility to ischemia/reperfusion injury (IRI). Matrix metalloproteinase-9 (MMP-9), an inducible gelatinase, is emerging as a central mediator of leukocyte traffic into inflamed tissues. However, its role in steatotic hepatic IRI has yet to be demonstrated.
methodsWe examined the function of MMP-9 in mice fed with a high-fat diet (HFD), which developed approximately 50% hepatic steatosis, predominantly macrovesicular, prior to partial hepatic IRI.
resultsThe inability of MMP-9(-/-) deficient steatotic mice to express MMP-9 significantly protected these mice from liver IRI. Compared to fatty controls, MMP-9(-/-) steatotic livers showed significantly reduced leukocyte infiltration, proinflammatory cytokine expression, and liver necrosis. Loss of MMP-9 activity preserved platelet endothelial cell adhesion molecule-1 (PECAM-1) expression, a modulator of vascular integrity at the endothelial cell-cell junctions in steatotic livers after IRI. Using in vitro approaches, we show that targeted inhibition of MMP-9 sheltered the extracellular portion of PECAM-1 from proteolytic processing, and disrupted leukocyte migration across this junctional molecule. Moreover, the evaluation of distinct parameters of regeneration, proliferating cell nuclear antigen (PCNA) and histone H3 phosphorylation (pH3), provided evidence that hepatocyte progression into S phase and mitosis was notably enhanced in MMP-9(-/-) steatotic livers after IRI.
conclusionsMMP-9 activity disrupts vascular integrity at least partially through a PECAM-1 dependent mechanism and interferes with regeneration of steatotic livers after IRI. Our novel findings establish MMP-9 as an important mediator of steatotic liver IRI.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.