ArticleBlood2016
Limiting hepatic Bmp-Smad signaling by matriptase-2 is required for erythropoietin-mediated hepcidin suppression in mice.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 93 citations in OpenAlex.
- HFE-Related Hemochromatosis May Be a Primary Kupffer Cell Disease.Biomedicines · 2025Review
- Role of Ferroptosis in ALD: Focusing on Hepcidin and Besides Hepcidin.Current medicinal chemistry · 2025Review
- A human anti-matriptase-2 antibody limits iron overload, α-globin aggregates, and splenomegaly in β-thalassemic mice.Blood advances · 2024Article
- Activation of Intestinal HIF2α Ameliorates Iron-Refractory Anemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- TMPRSS6 as a Therapeutic Target for Disorders of Erythropoiesis and Iron Homeostasis.Advances in therapy · 2023Review
- Iron metabolism and ferroptosis in type 2 diabetes mellitus and complications: mechanisms and therapeutic opportunities.Cell death & disease · 2023Review
- Alkaloid fraction ofSaudi journal of biological sciences · 2023Article
- Review
- The mutual crosstalk between iron and erythropoiesis.International journal of hematology · 2022Review
- Iron Mining for Erythropoiesis.International journal of molecular sciences · 2022Review
- TMPRSS12 Functions in Meiosis and Spermiogenesis and Is Required for Male Fertility in Mice.Frontiers in cell and developmental biology · 2022Article
- Physiology and Inflammation Driven Pathophysiology of Iron Homeostasis-Mechanistic Insights into Anemia of Inflammation and Its Treatment.Nutrients · 2021Review
- Erythroferrone and hepcidin as mediators between erythropoiesis and iron metabolism during allogeneic hematopoietic stem cell transplant.American journal of hematology · 2021Article
- Physiological and pathophysiological mechanisms of hepcidin regulation: clinical implications for iron disorders.British journal of haematology · 2021Review
- The pyruvate kinase activator mitapivat reduces hemolysis and improves anemia in a β-thalassemia mouse model.The Journal of clinical investigation · 2021Article
- Article
- Endoplasmic reticulum stress controls iron metabolism through TMPRSS6 repression and hepcidin mRNA stabilization by RNA-binding protein HuR.Haematologica · 2021Article
- Matriptase-2 and Hemojuvelin in Hepcidin Regulation: In Vivo Immunoblot Studies inInternational journal of molecular sciences · 2021Article
- [Expression of iron-regulating erythroid factors in different types of erythropoiesis disorders].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2021Article
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15 authors at 8 institutions in 3 countries.
Funding
Abstract
Hepcidin, the main regulator of iron homeostasis, is repressed when erythropoiesis is acutely stimulated by erythropoietin (EPO) to favor iron supply to maturing erythroblasts. Erythroferrone (ERFE) has been identified as the erythroid regulator that inhibits hepcidin in stress erythropoiesis. A powerful hepcidin inhibitor is the serine protease matriptase-2, encoded by TMPRSS6, whose mutations cause iron refractory iron deficiency anemia. Because this condition has inappropriately elevated hepcidin in the presence of high EPO levels, a role is suggested for matriptase-2 in EPO-mediated hepcidin repression. To investigate the relationship between EPO/ERFE and matriptase-2, we show that EPO injection induces Erfe messenger RNA expression but does not suppress hepcidin in Tmprss6 knockout (KO) mice. Similarly, wild-type (WT) animals, in which the bone morphogenetic protein-mothers against decapentaplegic homolog (Bmp-Smad) pathway is upregulated by iron treatment, fail to suppress hepcidin in response to EPO. To further investigate whether the high level of Bmp-Smad signaling of Tmprss6 KO mice counteracts hepcidin suppression by EPO, we generated double KO Bmp6-Tmprss6 KO mice. Despite having Bmp-Smad signaling and hepcidin levels that are similar to WT mice under basal conditions, double KO mice do not suppress hepcidin in response to EPO. However, pharmacologic downstream inhibition of the Bmp-Smad pathway by dorsomorphin, which targets the BMP receptors, improves the hepcidin responsiveness to EPO in Tmprss6 KO mice. We concluded that the function of matriptase-2 is dominant over that of ERFE and is essential in facilitating hepcidin suppression by attenuating the BMP-SMAD signaling.
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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.