ArticlePloS one2016
Heparanase Overexpression Reduces Hepcidin Expression, Affects Iron Homeostasis and Alters the Response to Inflammation.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 19 citations in OpenAlex.
- The Role of Particle Inhalation in Idiopathic Pulmonary Fibrosis.International journal of molecular sciences · 2025Review
- Current Landscape of Hepcidin Therapeutics.Advances in experimental medicine and biology · 2025Review
- Heparan sulfate chains in hepatocellular carcinoma.Gastroenterology report · 2025Review
- Mucus increases cell iron uptake to impact the release of pro-inflammatory mediators after particle exposure.Scientific reports · 2023Article
- Biology of the Heparanase-Heparan Sulfate Axis and Its Role in Disease Pathogenesis.Seminars in thrombosis and hemostasis · 2021Review
- Heparanase Level and Procoagulant Activity Are Increased in Thalassemia and Attenuated by Janus Kinase 2 Inhibition.The American journal of pathology · 2020Article
- Host-Pathogen Interaction as a Novel Target for Host-Directed Therapies in Tuberculosis.Frontiers in immunology · 2020Review
- α-Synuclein in blood cells differentiates Parkinson's disease from healthy controls.Annals of clinical and translational neurology · 2019Article
- Hepatic heparan sulfate is a master regulator of hepcidin expression and iron homeostasis in human hepatocytes and mice.The Journal of biological chemistry · 2019Article
- Systemic LPS-induced Aβ-solubilization and clearance in AβPP-transgenic mice is diminished by heparanase overexpression.Scientific reports · 2019Article
- Correlation of insulin-resistance with blood fat and glucose in elder patients after surgery for hepatic carcinoma.Experimental and therapeutic medicine · 2019Article
- Article
- Heparin inhibits intracellular Mycobacterium tuberculosis bacterial replication by reducing iron levels in human macrophages.Scientific reports · 2018Article
- Non-Anticoagulant Heparins Are Hepcidin Antagonists for the Treatment of Anemia.Molecules (Basel, Switzerland) · 2017Review
- Cigarette Smoke Particle-Induced Lung Injury and Iron Homeostasis.International journal of chronic obstructive pulmonary diseaseReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Hepcidin is the key regulator of systemic iron availability that acts by controlling the degradation of the iron exporter ferroportin. It is expressed mainly in the liver and regulated by iron, inflammation, erythropoiesis and hypoxia. The various agents that control its expression act mainly via the BMP6/SMAD signaling pathway. Among them are exogenous heparins, which are strong hepcidin repressors with a mechanism of action not fully understood but that may involve the competition with the structurally similar endogenous Heparan Sulfates (HS). To verify this hypothesis, we analyzed how the overexpression of heparanase, the HS degrading enzyme, modified hepcidin expression and iron homeostasis in hepatic cell lines and in transgenic mice. The results showed that transient and stable overexpression of heparanase in HepG2 cells caused a reduction of hepcidin expression and of SMAD5 phosphorylation. Interestingly, the clones showed also altered level of TfR1 and ferritin, indices of a modified iron homeostasis. The heparanase transgenic mice showed a low level of liver hepcidin, an increase of serum and liver iron with a decrease in spleen iron content. The hepcidin expression remained surprisingly low even after treatment with the inflammatory LPS. The finding that modification of HS structure mediated by heparanase overexpression affects hepcidin expression and iron homeostasis supports the hypothesis that HS participate in the mechanisms controlling hepcidin expression.
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.