ArticleThe Journal of biological chemistry2016
Transforming Growth Factor β1 (TGF-β1) Activates Hepcidin mRNA Expression in Hepatocytes.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis.Communications biology · 2021Pooled it
- Hepcidin as a Biomarker of Response to Antifibrotic Therapy in Idiopathic Pulmonary Fibrosis.Journal of clinical medicine · 2026Article
- The role of microglia in neurodegenerative diseases: from the perspective of ferroptosis.Acta pharmacologica Sinica · 2025Review
- Assessment of Cytokines TNF-alpha, IFN-gamma, TGF-beta-1, and IL-10 in Malaria Patients of the River Nile State , Sudan: A critical study of immune response.BMC immunology · 2025Article
- The Role of Macrophage Polarization and Ferroptosis in the Progression of Liver Fibrosis.Canadian journal of gastroenterology & hepatology · 2025Review
- Dual signaling pathways of TGF-β superfamily cytokines in hepatocytes: balancing liver homeostasis and disease progression.Frontiers in pharmacology · 2025Review
- Interplay between gut microbiota and the master iron regulator, hepcidin, in the pathogenesis of liver fibrosis.Pathogens and disease · 2024Review
- Iron metabolism and chronic inflammation in IgA nephropathy.Renal failure · 2023Review
- Article
- Iron as a therapeutic target in chronic liver disease.World journal of gastroenterology · 2023Review
- Novel Insights into Alcoholic Liver Disease: Iron Overload, Iron Sensing and Hemolysis.Journal of translational internal medicine · 2022Article
- IL-6 Regulates Hepcidin Expression Via the BMP/SMAD Pathway by Altering BMP6, TMPRSS6 and TfR2 Expressions at Normal and Inflammatory Conditions in BV2 Microglia.Neurochemical research · 2021Article
- Review
- Hepcidin secretion was not directly proportional to intracellular iron-loading in recombinant-TfR1 HepG2 cells: short communication.Molecular and cellular biochemistry · 2020Article
- TGFβ2-Hepcidin Feed-Forward Loop in the Trabecular Meshwork Implicates Iron in Glaucomatous Pathology.Investigative ophthalmology & visual science · 2020Article
- Endoscopic resection of the pancreatic tail and subsequent wound healing mechanisms in a porcine model.World journal of gastroenterology · 2019Article
- Iron and liver fibrosis: Mechanistic and clinical aspects.World journal of gastroenterology · 2019Review
- Article
- HepaticBlood · 2018Article
- Ethanol sensitizes hepatocytes for TGF-β-triggered apoptosis.Cell death & disease · 2018Article
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 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hepatic hormone hepcidin is the master regulator of systemic iron homeostasis. Its expression level is adjusted to alterations in iron levels, inflammatory cues, and iron requirements for erythropoiesis. Bone morphogenetic protein 6 (BMP6) contributes to the iron-dependent control of hepcidin. In addition, TGF-β1 may stimulate hepcidin mRNA expression in murine hepatocytes and human leukocytes. However, receptors and downstream signaling proteins involved in TGF-β1-induced hepcidin expression are still unclear. Here we show that TGF-β1 treatment of mouse and human hepatocytes, as well as ectopic expression of TGF-β1 in mice, increases hepcidin mRNA levels. The hepcidin response to TGF-β1 depends on functional TGF-β1 type I receptor (ALK5) and TGF-β1 type II receptor (TβRII) and is mediated by a noncanonical mechanism that involves Smad1/5/8 phosphorylation. Interestingly, increasing availability of canonical Smad2/3 decreases TGF-β1-induced hepcidin regulation, whereas the BMP6-hepcidin signal was enhanced, indicating a signaling component stoichiometry-dependent cross-talk between the two pathways. Although ALK2/3-dependent hepcidin activation by BMP6 can be modulated by each of the three hemochromatosis-associated proteins: HJV (hemojuvelin), HFE (hemochromatosis protein), and TfR2 (transferrin receptor 2), these proteins do not control the ALK5-mediated hepcidin response to TGF-β1. TGF-β1 mRNA levels are increased in mouse models of iron overload, indicating that TGF-β1 may contribute to hepcidin synthesis under these conditions. In conclusion, these data demonstrate that a complex regulatory network involving TGF-β1 and BMP6 may control the sensing of systemic and/or hepatic iron levels.
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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.