Endoplasmic reticulum stress controls iron metabolism through TMPRSS6 repression and hepcidin mRNA stabilization by RNA-binding protein HuR

International audienceThe liver hormone hepcidin controls the main inflowsof iron into plasma by binding to and inducing the degra-dation or the occlusion of the iron export activity of fer-roportin, the only known cellular exporter of iron.1,2When hepcidin concentrations are high, iron is trapped inenterocytes of the duodenum, hepatocytes, andmacrophages. Hepcidin production by the hepatocytes isinduced by a number of stimuli, most notably iron,through the BMP-SMAD signaling pathway,3 and inflam-matory signals, through the IL-6/ STAT3 signaling axis.4In addition, hepcidin has also been reported to respondto intracellular stress, namely endoplasmic reticulum (ER)stress which is involved in a number of pathophysiologi-cal states, including the inflammatory response, nutrientdisorders and viral infection. A previous study has sug-gested that hepcidin induction by ER stress is controlledby the BMP-SMAD pathway,5 but the exact mechanismis still uncertai