New modes of hepcidin regulation
In a Basic Science-in-Focus session Dr. Hal Drakesmith (University of Oxford, UK) discussed new modes of (epigenetic) regulation of the iron control hormone hepcidin and the control of hepcidin and iron toxicity by the redox-sensitive transcription factor Nrf2.
“Suppression of hepcidin by either iron deficiency or enhanced erythropoiesis converge by altering epigenetic marks on promoter-associated chromatin. We discovered that histondeacylase-3 (HDAC3) is required to decrease hepcidin transcription. HDAC-inhibitor panobisostat rescues hepcidin suppression in vivo and HDAC inhibition raises hepcidin in disease models of hepcidin suppression.”
Iron controls the expression of bone morphogenetic protein 6 (Bmp6). “We hypothesized that iron induces Bmp6 via oxidative stress and Nrf2.” His research revealed that Nrf2 is a ‘toxic iron’ sensor, orchestrating antioxidant defenses, but also regulating systemic iron homeostasis via control of Bmp6/hepcidin. “The Nfr/Bmp6/hepcidin axis is a therapeutic target.”