ArticleEndocrinology2016
Activin B Induces Noncanonical SMAD1/5/8 Signaling via BMP Type I Receptors in Hepatocytes: Evidence for a Role in Hepcidin Induction by Inflammation in Male Mice.
Article in Endocrinology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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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
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Pooled it
- Hypoferremic Response to Chronic Inflammation Is Controlled via the Hemojuvelin/Hepcidin/Ferroportin Axis and Does Not Involve Hepcidin-Independent Regulation of Fpn mRNA.American journal of hematology · 2025Article
- Activin B improves glucose metabolism via induction of Fgf21 and hepatic glucagon resistance.Nature communications · 2025Article
- Inflammatory indexes and anemia in chronic kidney disease: correlation and survival analysis of the National Health and Nutrition Examination Survey 2005-2018.Renal failure · 2024Article
- Inhibin subunit beta B (INHBB): an emerging role in tumor progression.Journal of physiology and biochemistry · 2024Review
- Hepatocyte activation and liver injury following cerebral ischemia promote HMGB1-mediated hepcidin upregulation in hepatocytes and regulation of systemic iron levels.Experimental & molecular medicine · 2024Article
- Bone morphogenetic protein 6 induces downregulation of pentraxin 3 expression in human granulosa lutein cells in women with polycystic ovary syndrome.Journal of assisted reproduction and genetics · 2024Article
- Iron metabolism and chronic inflammation in IgA nephropathy.Renal failure · 2023Review
- Inactivating the Uninhibited: The Tale of Activins and Inhibins in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2023Review
- Evolving roles of activins and inhibins in ovarian cancer pathophysiology.American journal of physiology. Cell physiology · 2023Review
- Reciprocal SOX2 regulation by SMAD1-SMAD3 is critical for anoikis resistance and metastasis in cancer.Cell reports · 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
- 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
- Physiology and Inflammation Driven Pathophysiology of Iron Homeostasis-Mechanistic Insights into Anemia of Inflammation and Its Treatment.Nutrients · 2021Review
- 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
- Treatment of anemia in difficult-to-manage patients with chronic kidney disease.Kidney international supplements · 2021Article
- Receptor binding competition: A paradigm for regulating TGF-β family action.Cytokine & growth factor reviews · 2021Review
- Profiling Activins and Follistatin in Colorectal Cancer According to Clinical Stage, Tumour Sidedness and Smad4 Status.Pathology oncology research : POR · 2021Article
- Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Induction of the iron regulatory hormone hepcidin contributes to the anemia of inflammation. Bone morphogenetic protein 6 (BMP6) signaling is a central regulator of hepcidin expression in the liver. Recently, the TGF-β/BMP superfamily member activin B was implicated in hepcidin induction by inflammation via noncanonical SMAD1/5/8 signaling, but its mechanism of action and functional significance in vivo remain uncertain. Here, we show that low concentrations of activin B, but not activin A, stimulate prolonged SMAD1/5/8 signaling and hepcidin expression in liver cells to a similar degree as canonical SMAD2/3 signaling, and with similar or modestly reduced potency compared with BMP6. Activin B stimulates hepcidin via classical activin type II receptors ACVR2A and ACVR2B, noncanonical BMP type I receptors activin receptor-like kinase 2 and activin receptor-like kinase 3, and SMAD5. The coreceptor hemojuvelin binds to activin B and facilitates activin B-SMAD1/5/8 signaling. Activin B-SMAD1/5/8 signaling has some selectivity for hepatocyte-derived cells and is not enabled by hemojuvelin in other cell types. Liver activin B mRNA expression is up-regulated in multiple mouse models of inflammation associated with increased hepcidin and hypoferremia, including lipopolysaccharide, turpentine, and heat-killed Brucella abortus models. Finally, the activin inhibitor follistatin-315 blunts hepcidin induction by lipopolysaccharide or B. abortus in mice. Our data elucidate a novel mechanism for noncanonical SMAD activation and support a likely functional role for activin B in hepcidin stimulation during inflammation in vivo.
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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.