ArticleThe American journal of pathology2007
Erythrophagocytosis by liver macrophages (Kupffer cells) promotes oxidative stress, inflammation, and fibrosis in a rabbit model of steatohepatitis: implications for the pathogenesis of human nonalcoholic steatohepatitis.
Article in The American journal of pathology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 154 citations in OpenAlex.
- The Red Blood Cell-Liver Axis: A New Framework for Iron Homeostasis and Liver Biology.Biology · 2026Article
- Eryptosis in Liver Diseases: Contribution to Anemia and Hypercoagulation.Medical sciences (Basel, Switzerland) · 2025Review
- Current understanding of eryptosis: mechanisms, physiological functions, role in disease, pharmacological applications, and nomenclature recommendations.Cell death & disease · 2025Review
- The impact of dietary neem leaf on the growth and biochemical traits of rabbits.Scientific reports · 2025Article
- Article
- Molecular and Immunometabolic Landscape of Erythrophagocytosis-induced Ferroptosis.Cardiovascular & hematological disorders drug targets · 2025Review
- The Molecular Determinants of Erythrocyte Removal Impact the Development of Metabolic Dysfunction-Associated Steatohepatitis.Endocrine, metabolic & immune disorders drug targets · 2025Review
- Reduced Erythrocyte Opsonization by Calreticulin, Lactadherin, Mannose-binding Lectin, and Thrombospondin-1 in MAFLD Patients.Cardiovascular & hematological disorders drug targets · 2025Article
- Review
- The role of body mass index on the association between the energy-adjusted dietary inflammatory index and hyperuricemia: a mediation analysis based on NHANES (2007-2016).International journal of obesity (2005) · 2024Article
- Erythrocyte-brain endothelial interactions induce microglial responses and cerebral microhemorrhages in vivo.Journal of neuroinflammation · 2023Article
- Pharmacological Prevention of Ectopic Erythrophagocytosis by Cilostazol Mitigates Ferroptosis in NASH.International journal of molecular sciences · 2023Article
- Iron as a therapeutic target in chronic liver disease.World journal of gastroenterology · 2023Review
- Unexplored Roles of Erythrocytes in Atherothrombotic Stroke.Neurology international · 2023Review
- Defining newly formed and tissue-resident bone marrow-derived macrophages in adult mice based on lysozyme expression.Cellular & molecular immunology · 2022Article
- Possible Role of Extracellular Vesicles in Hepatotoxicity of Acetaminophen.International journal of molecular sciences · 2022Article
- Red Blood Cell-Conditioned Media from Non-Alcoholic Fatty Liver Disease Patients Contain Increased MCP1 and Induce TNF-α Release.Reports of biochemistry & molecular biology · 2022Article
- Iron overload in alcoholic liver disease: underlying mechanisms, detrimental effects, and potential therapeutic targets.Cellular and molecular life sciences : CMLS · 2022Review
- Ironing Out the Details: How Iron Orchestrates Macrophage Polarization.Frontiers in immunology · 2021Review
- Red Blood Cell Dysfunction in Non-Alcoholic Fatty Liver Disease: Marker and Mediator of Molecular Mechanisms.Maedica · 2020Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonalcoholic steatohepatitis (NASH) is a progressive fibrotic disease, the pathogenesis of which has not been fully elucidated. Here, we report a molecular aspect of this disease elucidated using rabbits fed a cholesterol-rich high-fat diet and exhibiting insulin resistance. The liver in this model showed steatohepatitis with fibrosis and high mRNA expression for some cytokines, heme oxygenase-1, transforming growth factor-beta1, and collagen alpha1(I). Erythrocytes isolated from the model showed marked fragility and the externalization of phosphatidylserine (PS) on the outer leaflet of the membrane and were frequently engulfed by Kupffer cells/macrophages in the hepatic sinusoids. Expression of milk fat globule-epidermal growth factor (EGF)-factor 8, a PS-binding protein, was augmented in the liver. In culture, RAW 264.7 cells engulfed erythrocytes oxidized by tert-butyl hydroperoxide, a process that was inhibited by anti-milk fat globule-EGF-factor 8 antibody. In addition, PS-positive erythrocytes appeared entrapped in the model liver in ex vivo perfusion experiments. Finally, in specimens from NASH patients, the aggregation of erythrocytes in inflammatory hepatic sinusoids was notable. These results indicate that the engulfment of PS-externalized, apoptotic signal-positive, erythrocytes by hepatic macrophages may lead to the deposition of iron derived from hemoglobin in the liver and be involved in the pathogenesis of steatohepatitis.
Indexed as
Identifiers
What OpenQuestion holds
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.