ArticleNature metabolism2020
c-Rel orchestrates energy-dependent epithelial and macrophage reprogramming in fibrosis.
Erratum issuedOpen access · greenAbstract read
In one paragraph
Article in Nature metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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20citing papers in PubMed
1.8field-weighted citation impact, top 14% of its field
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- Macrophage heterogeneity in organ fibrosis in the era of single-cell omics.Molecular biology reports · 2026Review
- RelJournal of translational medicine · 2026Article
- Targeting macrophage function with botulinum toxin: a novel translational strategy for preventing and treating pathological scars.Postepy dermatologii i alergologii · 2026Review
- c-Rel drives pancreatic cancer metastasis through fibronectin-integrin signaling-induced isolation stress resistance and EMT.Molecular cancer · 2025Article
- Sodium nitrate protects against metabolic syndrome by sialin-mediated macrophage rebalance.Signal transduction and targeted therapy · 2025Article
- Pharmacological manipulation of liver fibrosis progression using novel HDAC6 inhibitors.The FEBS journal · 2025Article
- Deficiency of myeloid NPC1 exacerbates liver injury and fibrosis by impairing macrophage efferocytosis.Journal of advanced research · 2025Article
- Endothelial c-REL orchestrates atherosclerosis at regions of disturbed flow through crosstalk with TXNIP-p38 and non-canonical NF-κB pathways.Cardiovascular research · 2025Article
- YTHDC2 manipulates anti-tumoral macrophage polarization and predicts favorable outcomes in triple negative breast cancer.NPJ precision oncology · 2025Article
- Novel regulators of hepatic macrophages in liver fibrosis.Frontiers in immunology · 2025Review
- Hepatocellular senescence induces multi-organ senescence and dysfunction via TGFβ.Nature cell biology · 2024Article
- Advances in the understanding of the role and mechanism of action of PFKFB3‑mediated glycolysis in liver fibrosis (Review).International journal of molecular medicine · 2024Review
- DPSCs regulate epithelial-T cell interactions in oral submucous fibrosis.Stem cell research & therapy · 2024Article
- The E3 ubiquitin ligase RNF115 regulates phagosome maturation and host response to bacterial infection.The EMBO journal · 2022Article
- IGFBP5 promotes diabetic kidney disease progression by enhancing PFKFB3-mediated endothelial glycolysis.Cell death & disease · 2022Article
- Role of CCR2-Positive Macrophages in Pathological Ventricular Remodelling.Biomedicines · 2022Review
- Pathogenesis of Liver Fibrosis and Its TCM Therapeutic Perspectives.Evidence-based complementary and alternative medicine : eCAM · 2022Review
- DNA Methylome Alterations Are Associated with Airway Macrophage Differentiation and Phenotype during Lung Fibrosis.American journal of respiratory and critical care medicine · 2021Article
- Protective Effect of Oligonol on Dimethylnitrosamine-Induced Liver Fibrosis in Rats via the JNK/NF-κB and PI3K/Akt/Nrf2 Signaling Pathways.Antioxidants (Basel, Switzerland) · 2021Article
- Nanotechnology in Drug Delivery for Liver Fibrosis.Frontiers in molecular biosciences · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
42 authors at 10 institutions in 6 countries.
Jack LeslieNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. jack.leslie@newcastle.ac.uk.ORCID http://orcid.org/0000-0001-6443-2396
Marina García MaciaNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0002-3908-9060
Saimir LuliNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Julie C WorrellNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0001-7754-1364
William J ReillyNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Hannah L PaishNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Amber KnoxNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Ben S BarksbyNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Lucy M GeeNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Marco Y W ZakiNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0003-3097-5776
Amy L CollinsNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0003-3619-2588
Rachel A BurgoyneNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Rainie CameronNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Charlotte BraggNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Xin XuNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Git W ChungNewcells Biotech, The Biosphere, Newcastle Helix, Newcastle upon Tyne, UK.
Colin D A BrownNewcells Biotech, The Biosphere, Newcastle Helix, Newcastle upon Tyne, UK.
Andrew D BlanchardFibrosis Discovery Performance Unit, Respiratory Therapy Area, Medicines Research Centre, GlaxoSmithKline R&D, Stevenage, UK.
Carmel B NanthakumarFibrosis Discovery Performance Unit, Respiratory Therapy Area, Medicines Research Centre, GlaxoSmithKline R&D, Stevenage, UK.
Morten KarsdalNordic Bioscience A/S, Biomarkers & Research, Herlev, Denmark.
Stuart M RobinsonDepartment of Hepatobiliary Surgery, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Derek M ManasDepartment of Hepatobiliary Surgery, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Gourab SenDepartment of Hepatobiliary Surgery, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Jeremy FrenchDepartment of Hepatobiliary Surgery, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Steven A WhiteDepartment of Hepatobiliary Surgery, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Sandra MurphyNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0002-1130-9295
Matthias TrostNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0002-5732-700X
Johannes L ZakrzewskiCenter for Discovery and Innovation and John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA.
Ulf KleinDivision of Haematology & Immunology, Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.ORCID http://orcid.org/0000-0002-4789-967X
Robert F SchwabeDepartment of Medicine, Columbia University, New York, NY, USA.
Ingmar MederackeDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.ORCID http://orcid.org/0000-0003-2592-7171
Colin NixonCancer Research UK Beatson Institute, Garscube Estate, Glasgow, UK.ORCID http://orcid.org/0000-0002-8085-2160
Tom BirdCancer Research UK Beatson Institute, Garscube Estate, Glasgow, UK.ORCID http://orcid.org/0000-0002-6120-1581
Laure-Anne TeuwenLaboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven, Belgium.
Luc SchoonjansLaboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven, Belgium.
Peter CarmelietLaboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven, Belgium.ORCID http://orcid.org/0000-0001-7961-1821
Jelena MannNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Andrew J FisherNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0003-4822-7223
Neil S SheerinNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Lee A BorthwickNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Derek A MannNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Fiona OakleyNewcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. fiona.oakley@newcastle.ac.uk.ORCID http://orcid.org/0000-0001-8692-1836
Newcastle University · GBNewcastle upon Tyne Hospitals NHS Foundation Trust · GBVIB-KU Leuven Center for Cancer Biology · BECancer Research UK Scotland Institute · GBGlaxoSmithKline (United Kingdom) · GBColumbia University · USHackensack University Medical Center · USMedizinische Hochschule Hannover · DENordic Bioscience (Denmark) · DKUniversity of Leeds · GB
Funding
Cancer Research UK 23390Cancer Research UK 26813Cancer Research UK A171196Cancer Research UK A23390Cancer Research UK A26813Medical Research Council G0401643Medical Research Council G0700890Medical Research Council G0900535Medical Research Council L016354Medical Research Council MC_PC_14101Medical Research Council MR/K001949/1Medical Research Council MR/K0019494/1Medical Research Council MR/L016354/1Medical Research Council MR/R023026/1National Centre for the Replacement, Refinement and Reduction of Animals in Research NC/K000748/1Versus Arthritis 20812Wellcome Trust 087961Wellcome Trust WT107492Z
Abstract
Fibrosis is a common pathological feature of chronic disease. Deletion of the NF-κB subunit c-Rel limits fibrosis in multiple organs, although the mechanistic nature of this protection is unresolved. Using cell-specific gene-targeting manipulations in mice undergoing liver damage, we elucidate a critical role for c-Rel in controlling metabolic changes required for inflammatory and fibrogenic activities of hepatocytes and macrophages and identify Pfkfb3 as the key downstream metabolic mediator of this response. Independent deletions of Rel in hepatocytes or macrophages suppressed liver fibrosis induced by carbon tetrachloride, while combined deletion had an additive anti-fibrogenic effect. In transforming growth factor-β1-induced hepatocytes, c-Rel regulates expression of a pro-fibrogenic secretome comprising inflammatory molecules and connective tissue growth factor, the latter promoting collagen secretion from HMs. Macrophages lacking c-Rel fail to polarize to M1 or M2 states, explaining reduced fibrosis in Rel
Indexed as
AnimalsCell PolarityEpitheliumGene TargetingHepatocytesHydroxyprolineLiver CirrhosisLiver RegenerationMacrophagesMiceMice, Inbred C57BLMice, KnockoutMitosisParacrine CommunicationPhosphofructokinase-2Proto-Oncogene Proteins c-relHydroxyprolinePFKFB3 protein, mousePhosphofructokinase-2Proto-Oncogene Proteins c-relREL protein, human
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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.