Intestinal Ferritin H Is Required for an Accurate Control of Iron Absorption

Abstract

To maintain appropriate body iron levels, iron absorption by the proximal duodenum is thought to be controlled by hepcidin, a polypeptide secreted by hepatocytes in response to high serum iron. Hepcidin limits basolateral iron efflux from the duodenal epithelium by binding and downregulating the intestinal iron exporter ferroportin. Here, we found that mice with an intestinal ferritin H gene deletion show increased body iron stores and transferrin saturation. As expected for iron-loaded animals, the ferritin H-deleted mice showed induced liver hepcidin mRNA levels and reduced duodenal expression of DMT1 and DcytB mRNA. In spite of these feedback controls, intestinal ferroportin protein and (59)Fe absorption were increased more than 2-fold in the deleted mice. Our results demonstrate that hepcidin-mediated regulation alone is insufficient to restrict iron absorption and that intestinal ferritin H is also required to limit iron efflux from intestinal cells.

Proximal tubule H-ferritin mediates iron trafficking in acute kidney injury

“…Additionally, HO-1 induction was coupled to increased ferritin expression during AKI (8,10). Consistent with recent findings in the intestine, our results revealed that deletion of FtH was accompanied by a significant increase in HO-1 expression under both basal and AKI conditions, presumably as an antioxidant compensatory mechanism (24). However, despite significantly higher levels of HO-1 in FtH PT-/-kidneys, AKI severity was remarkably higher in these animals compared with their control littermates.…”

“…Additionally, whereas the contribution of the intestine, liver, and reticuloendothelial system in systemic iron homeostasis is extensively studied, very little is known about the extent of renal involvement in such orchestration (22)(23)(24)(25)(26)(27)(28). Considering the wealth of knowledge regarding renal handling of assorted molecules and electrolytes, animal models that would enable deciphering the role of the kidney in systemic iron homeostasis and iron trafficking during AKI are timely and may provide new avenues for potential therapies.…”

Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women

“…This may be because of the relatively low analytical and biological variation in PF and sTfR compared with PHep, the high correlation of BIS with PHep in healthy subjects, and/or the possibility that BIS (PF/sTfR) reflect a different pathway of cellular iron regulation, independent from systemic signals. 35,36 In the models predicting the first-dose absorption, only BIS was a significant predictor and not hepcidin. By contrast, for absorption of the second dose, both BIS and PHep are predictors of absorption, and overall prediction increased (R 2 5 0.791 vs R 2 5 0.650) relative to the first dose.…”

Biology of ferritin in mammals: an update on iron storage, oxidative damage and neurodegeneration

“…Increased LIP and ROS and mitochondrial depolarization were observed in lymphocytes form mice with Mx-Cre mediated conditional deletion (Vanoaica et al 2014); the survival and maturation of B-cells exposed to B-cell activating factor was reduced and partially rescued by iron chelation with deferiprone. Interestingly, the deletion of the gene in the intestine was associated with increased iron body stores and related parameters (transferrin saturation, hepatic hepcidin mRNA level); nonetheless intestinal iron absorption was twofold higher than in wild type animals, thus suggesting a role for ferritin in the "mucosal block", the balance between iron retained in the cells and the ones to be transferred through basolateral membrane (Vanoaica et al 2010). The storage and anti-oxidant action of cytosolic ferritin has been shown to exert a strong protective effect in different in vivo models of cellular/organ stress.…”