ArticleThe Journal of biological chemistry2011
Regulation of type II transmembrane serine proteinase TMPRSS6 by hypoxia-inducible factors: new link between hypoxia signaling and iron homeostasis.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis 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
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Pooled it
- Four-Week Studies of Oral Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor GSK1278863 for Treatment of Anemia.Journal of the American Society of Nephrology : JASN · 2016Trial
- Red Blood Cell Distribution Width Is a Biomarker of Red Cell Dysfunction Associated with Inflammation, Macrophage Polarization, and Coronary Artery Calcification: A Prognostic Marker in Cardiovascular Disease and a Potential Target for Anti-Cytokine Therapy.Life (Basel, Switzerland) · 2026Review
- Hepcidin as a Molecular Hub of Iron Homeostasis: From BMP-SMAD Signaling to Therapeutic Modulation.Biomolecules · 2026Review
- High‑altitude polycythemia: Unveiling the molecular landscape beyond erythropoietin (Review).International journal of molecular medicine · 2026Review
- Three distinct trajectories of red blood cell distribution width and their significant associations with mortality in sepsis patients: a group-based trajectory modeling study with validation.Frontiers in medicine · 2026Article
- Iron, the Essential Micronutrient: A Comprehensive Review of Regulatory Pathways of Iron Metabolism.Nutrients · 2025Review
- Targeting the Liver Serine Protease TMPRSS6 Ameliorates Steatosis and Attenuates Fibrosis in Experimental MASLD.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Red Blood Cell Distribution Width is a Biomarker of Red Cell Dysfunction Associated with High Systemic Inflammation and a Prognostic Marker in Heart Failure and Cardiovascular Disease: A Potential Predictor of Atrial Fibrillation Recurrence.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2024Review
- Iron deficiency and supplementation in heart failure.Nature reviews. Cardiology · 2024Review
- Red Blood Cell Distribution Width as a Biomarker of Red Cell Dysfunction Associated with Inflammation and Macrophage Iron Retention: A Prognostic Marker in Heart Failure and a Potential Predictor for Iron Replacement Responsiveness.Cardiac failure review · 2024Article
- Associated Effect ofMetabolites · 2022Article
- Novel Insights into Alcoholic Liver Disease: Iron Overload, Iron Sensing and Hemolysis.Journal of translational internal medicine · 2022Article
- Iron Mining for Erythropoiesis.International journal of molecular sciences · 2022Review
- Serum Erythroferrone During Pregnancy Is Related to Erythropoietin but Does Not Predict the Risk of Anemia.The Journal of nutrition · 2021Observational
- Article
- Article
- Inflammation Mediated Hepcidin-Ferroportin Pathway and Its Therapeutic Window in Breast Cancer.Breast cancer (Dove Medical Press) · 2020Review
- Regulation of Iron Homeostasis and Related Diseases.Mediators of inflammation · 2020Review
- Therapeutic Advances in Regulating the Hepcidin/Ferroportin Axis.Pharmaceuticals (Basel, Switzerland) · 2019Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepcidin is a liver-derived hormone with a key role in iron homeostasis. In addition to iron, it is regulated by inflammation and hypoxia, although mechanisms of hypoxic regulation remain unclear. In hepatocytes, hepcidin is induced by bone morphogenetic proteins (BMPs) through a receptor complex requiring hemojuvelin (HJV) as a co-receptor. Type II transmembrane serine proteinase (TMPRSS6) antagonizes hepcidin induction by BMPs by cleaving HJV from the cell membrane. Inactivating mutations in TMPRSS6 lead to elevated hepcidin levels and consequent iron deficiency anemia. Here we demonstrate that TMPRSS6 is up-regulated in hepatic cell lines by hypoxia and by other activators of hypoxia-inducible factor (HIF). We show that TMPRSS6 expression is regulated by both HIF-1α and HIF-2α. This HIF-dependent up-regulation of TMPRSS6 increases membrane HJV shedding and decreases hepcidin promoter responsiveness to BMP signaling in hepatocytes. Our results reveal a potential role for TMPRSS6 in hepcidin regulation by hypoxia and provide a new molecular link between oxygen sensing and iron homeostasis.
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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.