ArticleHepatology (Baltimore, Md.)2009
Ferritin functions as a proinflammatory cytokine via iron-independent protein kinase C zeta/nuclear factor kappaB-regulated signaling in rat hepatic stellate cells.
Article in Hepatology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers, 3 of them syntheses that pooled it.
What it found
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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
150 citing papers in PubMed, 3 syntheses or guidelines pooled it, 292 citations in OpenAlex.
- Clinical practice guidelines on hemochromatosis: Asian Pacific Association for the Study of the Liver.Hepatology international · 2023Guideline
- Update in Hyperferritinemic Syndromes: Recognition and Management - A Scoping Review.The Brown journal of hospital medicine · 2022Pooled it
- Bibliometrics analysis on the research status and trends of adult-onset Still's disease: 1921-2021.Frontiers in immunology · 2022Pooled it
- Ferritin, inflammation, and iron deficiency in acute heart failure: evidence from the EDIFICA cohort.Clinical research in cardiology : official journal of the German Cardiac Society · 2026Observational
- Dysregulated ferritin and iron homeostasis in autosomal dominant polycystic kidney disease.American journal of physiology. Renal physiology · 2026Article
- Association of iron status with gestational diabetes and preeclampsia in an obesogenic context: Results from a cohort of pregnant Chilean women.European journal of clinical nutrition · 2026Article
- Macrophage-Derived Ferritin Exacerbates Silica-Induced Pulmonary Fibrosis via PIK3R2-Mediated Fibroblast Differentiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Still's Disease and Autoinflammation: Positioning an Inflammatory Syndrome on the Autoinflammation-Autoimmunity Spectrum.Current rheumatology reports · 2026Review
- Hyperinflammation and immunomodulation in influenza, SARS-CoV-2 and syncytial respiratory virus infection in adults: from innate immune responses and biomarkers to clinical and therapeutic implications.Frontiers in microbiology · 2026Review
- Early hyperferritinemia in polytrauma: a biomarker of systemic inflammation and mortality risk in a multicenter cohort study.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Observational
- Hyperferritinemia and the Risk of Liver Fibrosis and Liver-Related Events in Patients with Type 2 Diabetes Mellitus and Metabolic Dysfunction-Associated Steatotic Liver Disease.Medicina (Kaunas, Lithuania) · 2025Article
- Epstein-Barr virus modulates iron metabolism and ferritin expression to promote tumorigenesis in gastric cancer.Journal of molecular histology · 2025Article
- Ferritin in Acute Myeloid Leukemia: Not Only a Marker of Inflammation and Iron Overload, but Also a Regulator of Cellular Iron Metabolism, Signaling and Communication.International journal of molecular sciences · 2025Review
- Ferritin's role in infectious diseases: Exploring pathogenic mechanisms and clinical implications.New microbes and new infections · 2025Review
- Ferritin Light Chain Alleviates Cerebral Ischemic-Reperfusion Injury-Induced Neuroinflammation via the HIF1α Mediated NF-κB Signaling Pathways.Inflammation · 2025Article
- [Effects of liver fibrosis induced by iron overload on M2 polarization of macrophages in mice].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Connexin 43 is downregulated in advanced Parkinson's disease in multiple brain regions which correlates with symptoms.Scientific reports · 2025Article
- Ferritin as an Effective Prognostic Factor and Potential Cancer Biomarker.Current issues in molecular biology · 2025Review
- Effect of parenteral L-carnitine in hospitalized patients with moderate to severe COVID-19: A randomized double-blind clinical trial.BioImpacts : BI · 2025Article
- Diagnostic Utility of Serum Ferritin in Identifying Liver Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD): A Cross-Sectional Study Using National Health and Nutrition Examination Survey (NHANES-2017-2020) Data.Indian journal of clinical biochemistry : IJCB · 2025Article
90 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
Abstract
unlabelledCirculating ferritin levels reflect body iron stores and are elevated with inflammation in chronic liver injury. H-ferritin exhibits a number of extrahepatic immunomodulatory properties, although its role in hepatic inflammation and fibrogenesis is unknown. Hepatic stellate cells respond to liver injury through production of proinflammatory mediators that drive fibrogenesis. A specific receptor for ferritin has been demonstrated on activated hepatic stellate cells, although its identity and its role in stellate cell activation is unclear. We propose that ferritin acts as a cytokine regulating proinflammatory function via nuclear factor kappaB (NF-kappaB)-regulated signaling in hepatic stellate cell biology. Hepatic stellate cells were treated with tissue ferritin and iron-free apoferritin, recombinant H-ferritins and L-ferritins, to assess the role of ferritin versus ferritin-bound iron in the production of proinflammatory mediators of fibrogenesis, and to determine whether signaling pathways act via a proposed H-ferritin endocytosis receptor, T cell immunoglobulin-domain and mucin-domain 2 (Tim-2). This study demonstrated that ferritin activates an iron-independent signaling cascade, involving Tim-2 independent phosphoinositide 3 (PI3)-kinase phosphorylation, protein kinase C zeta (PKCzeta) and p44/p42-mitogen-activated protein kinase, resulting in p50/p65-NF-kappaB activation and markedly enhanced expression of hepatic proinflammatory mediators interleukin-1beta (IL-1beta), inducible nitric oxide synthase (iNOS), regulated on activation normal T cell expressed and secreted (RANTES), inhibitor of kappa Balpha (IkappaBalpha), and intercellular adhesion molecule 1 (ICAM1).
conclusionsThis study has defined the role of ferritin as a proinflammatory mediator of hepatic stellate cell biology acting through the NF-kappaB signaling pathway, and suggests a potential role in the inflammatory processes associated with hepatic fibrogenesis.
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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.