Targeting the BMP Receptor Inhibitor FKBP12 to Upregulate Hepcidin in Wild-Type and Hemojuvelin-Hemochromatosis Models
نویسندگان
چکیده
منابع مشابه
BMP Signaling Modulates Hepcidin Expression in Zebrafish Embryos Independent of Hemojuvelin
Hemojuvelin (Hjv), a member of the repulsive-guidance molecule (RGM) family, upregulates transcription of the iron regulatory hormone hepcidin by activating the bone morphogenetic protein (BMP) signaling pathway in mammalian cells. Mammalian models have identified furin, neogenin, and matriptase-2 as modifiers of Hjv's function. Using the zebrafish model, we evaluated the effects of hjv and its...
متن کاملDefective targeting of hemojuvelin to plasma membrane is a common pathogenetic mechanism in juvenile hemochromatosis.
Hemojuvelin (HJV) positively modulates the iron regulator hepcidin, and its mutations are the major cause of juvenile hemochromatosis (JH), a recessive disease leading to iron overload. Defective HJV reduces hepcidin up-regulation both in humans and in Hjv-deficient mice. To investigate the JH pathogenesis and the functional properties of human HJV we studied the biosynthesis and maturation of ...
متن کاملHemojuvelin regulates hepcidin expression via a selective subset of BMP ligands and receptors independently of neogenin.
Hemojuvelin (HJV) is a coreceptor for bone morphogenetic protein (BMP) signaling that regulates hepcidin expression and iron metabolism. However, the precise combinations of BMP ligands and receptors used by HJV remain unknown. HJV has also been demonstrated to bind to neogenin, but it is not known whether this interaction has a role in regulating hepcidin expression. In the present study, we s...
متن کاملHFE interacts with the BMP type I receptor ALK3 to regulate hepcidin expression.
Mutations in HFE are the most common cause of hereditary hemochromatosis (HH). HFE mutations result in reduced expression of hepcidin, a hepatic hormone, which negatively regulates iron absorption from the duodenum and iron release from macrophages. However, the mechanism by which HFE regulates hepcidin expression in hepatocytes is not well understood. It is known that the bone morphogenetic pr...
متن کاملHemojuvelin N-terminal mutants reach the plasma membrane but do not activate the hepcidin response.
BACKGROUND Hemojuvelin is a glycosylphosphatidylinositol-anchored protein, expressed in liver, skeletal muscle and heart. As a co-receptor of bone morphogenetic protein, membrane hemojuvelin positively modulates the iron regulator hepcidin. Mutations of the gene encoding for hemojuvelin cause juvenile hemochromatosis, characterized by hepcidin deficiency and severe iron overload. We have previo...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Blood
سال: 2019
ISSN: 0006-4971,1528-0020
DOI: 10.1182/blood-2019-126496