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  • hepatocytes
  • Finally, we demonstrated, using hepatocytes isolated from Hfe −/− mice, that HFE was not critical for the hepcidin response to holotransferrin but important for basal hepcidin expression. (haematologica.org)
  • Conclusions We demonstrate that hepatocytes are liver iron-sensor cells and that transferrin receptor-2, by signaling through the ERK1/2 pathway, and bone morphogenetic protein/hemojuvelin, by signaling through the Smad pathways, coordinately regulate the iron-sensing machinery linking holotransferrin to hepcidin. (haematologica.org)
  • Increased erythropoietic activity in the BM produces growth differentiation factor 15 (GDF15) and erythroferrone, which have been shown suppress hepcidin in hepatocytes. (haaselab.org)
  • holotransferrin
  • Transferrin receptor-2 activation by its ligand holotransferrin led to extracellular signal regulated kinase (ERK)/mitogen activated protein kinase pathway stimulation and the ERK specific inhibitor U0-126 blunted holotransferrin-mediated induction of hepcidin. (haematologica.org)
  • Circulating factors (holotransferrin, cytokines, erythroid regulators) might variably contribute to hepcidin modulation in different pathological conditions. (pubmedcentralcanada.ca)
  • Stat3
  • Here we have shown that hepcidin-activated Jak2 also phosphorylates the transcription factor Stat3, resulting in a transcriptional response. (pubmedcentralcanada.ca)
  • Here we demonstrate that activation of Jak2, through binding of hepcidin to Fpn, results in Stat3-mediated transcriptional activation of a large number of genes. (pubmedcentralcanada.ca)
  • HAMP
  • HAMP mRNA expression in Huh-7 cells exposed to sera form C-Donors, HFE -HH and THAL reproduced, at lower level, the results observed in HepG2, suggesting the important but not critical role of HFE in hepcidin regulation. (pubmedcentralcanada.ca)
  • Circulating
  • b. to measure mRNA hepcidin expression in two different hepatic cell lines (HepG2 and Huh-7) exposed to patients and controls sera to assess whether circulating factors could influence hepcidin transcription in different pathological conditions. (pubmedcentralcanada.ca)
  • transcription
  • HJV acts as a co-receptor for bone morphogenetic protein (BMP) signaling, ultimately activating receptor Smad/Smad4 complexes to increase hepcidin transcription. (haematologica.org)
  • regulators
  • Several proteins have recently been identified to act as upstream regulators of hepcidin expression, such as HFE and hemojuvelin (HJV). (ucl.ac.uk)
  • molecules
  • Although hepcidin is regulated by iron, the molecules involved in this regulation and whether HFE is involved in this regulation remain to be clarified. (ucl.ac.uk)
  • receptor
  • Studies have shown that activation of Jak2, by growth factor or cytokine receptors, results in receptor phosphorylation as well as the phosphorylation of Stats, which are transcriptional activators ( 6 , 7 ). (pubmedcentralcanada.ca)
  • leads
  • Hepcidin binding to Fpn leads to the binding and activation of Jak2, which phosphorylates Fpn, resulting in its internalization through clathrin-coated pits ( 5 ). (pubmedcentralcanada.ca)