ArticleBlood2011
Tmprss6 is a genetic modifier of the Hfe-hemochromatosis phenotype in mice.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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.
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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.
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Who cites it
44 citing papers in PubMed, 83 citations in OpenAlex.
- Hepcidin mediates the disorder of iron homeostasis and mitochondrial function in mice under hypobaric hypoxia exposure.Apoptosis : an international journal on programmed cell death · 2025Article
- Control of Systemic Iron Homeostasis: Insights Gained from Studying Mouse Models.Advances in experimental medicine and biology · 2025Review
- Transmembrane serine protease 6, a novel target for inhibition of neuronal tumor growth.Cell death & disease · 2024Article
- Bone marrow sinusoidal endothelial cells are a site of Fgf23 upregulation in a mouse model of iron deficiency anemia.Blood advances · 2023Article
- TMPRSS6 as a Therapeutic Target for Disorders of Erythropoiesis and Iron Homeostasis.Advances in therapy · 2023Review
- Coordination of iron homeostasis by bone morphogenetic proteins: Current understanding and unanswered questions.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Article
- Article
- Iron distribution in different tissues of homozygous Mask (msk/msk) mice and the effects of oral iron treatments.American journal of hematology · 2021Article
- Review
- Gnpat does not play an essential role in systemic iron homeostasis in murine model.Journal of cellular and molecular medicine · 2020Article
- Iron overload and cirrhosis in referredCanadian liver journal · 2020Article
- SLN124, a GalNAc-siRNA Conjugate Targeting TMPRSS6, Efficiently Prevents Iron Overload in Hereditary Haemochromatosis Type 1.HemaSphere · 2019Article
- Animal Models of Normal and Disturbed Iron and Copper Metabolism.The Journal of nutrition · 2019Review
- Liver iron sensing and body iron homeostasis.Blood · 2019Review
- Effect of stimulated erythropoiesis on liver SMAD signaling pathway in iron-overloaded and iron-deficient mice.PloS one · 2019Article
- Hepcidin-ferroportin axis in health and disease.Vitamins and hormones · 2019Review
- Hepcidin Therapeutics.Pharmaceuticals (Basel, Switzerland) · 2018Review
- Smad7 deficiency decreases iron and haemoglobin through hepcidin up-regulation by multilayer compensatory mechanisms.Journal of cellular and molecular medicine · 2018Article
- Hepcidin agonists as therapeutic tools.Blood · 2018Review
- Matriptase-2 suppresses hepcidin expression by cleaving multiple components of the hepcidin induction pathway.The Journal of biological chemistry · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The hereditary hemochromatosis protein HFE promotes the expression of hepcidin, a circulating hormone produced by the liver that inhibits dietary iron absorption and macrophage iron release. HFE mutations are associated with impaired hepatic bone morphogenetic protein (BMP)/SMAD signaling for hepcidin production. TMPRSS6, a transmembrane serine protease mutated in iron-refractory iron deficiency anemia, inhibits hepcidin expression by dampening BMP/SMAD signaling. In the present study, we used genetic approaches in mice to examine the relationship between Hfe and Tmprss6 in the regulation of systemic iron homeostasis. Heterozygous loss of Tmprss6 in Hfe(-/-) mice reduced systemic iron overload, whereas homozygous loss caused systemic iron deficiency and elevated hepatic expression of hepcidin and other Bmp/Smad target genes. In contrast, neither genetic loss of Hfe nor hepatic Hfe overexpression modulated the hepcidin elevation and systemic iron deficiency of Tmprss6(-/-) mice. These results indicate that genetic loss of Tmprss6 increases Bmp/Smad signaling in an Hfe-independent manner that can restore Bmp/Smad signaling in Hfe(-/-) mice. Furthermore, these results suggest that natural genetic variation in the human ortholog TMPRSS6 might modify the clinical penetrance of HFE-associated hereditary hemochromatosis, raising the possibility that pharmacologic inhibition of TMPRSS6 could attenuate iron loading in this disorder.
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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.