Iron Imports. VI. HFE and regulation of intestinal iron absorption

Fleming, Robert E.; Britton, Robert S.

doi:10.1152/ajpgi.00486.2005

Cited by 40 publications

(26 citation statements)

References 40 publications

(39 reference statements)

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“…18 The binding sites of HFE and diferric Tf overlap. 56 HFE along with diferric-Tf-TfR1 complex is endocytosed during receptormediated endocytosis. 57 Despite iron overload, patients with HFE mutations and HFE-deficient mice show hepatic HepcmRNA levels below those of normal control mice, suggesting that HFE is required for Hepc gene expression; 58,59 however, Hepc gene expression was not completely abolished in HFEdeficient mice, indicating the existence of intact Hepc regulatory setup 60 in the absence of HFE.…”

Section: Discussionmentioning

confidence: 99%

Changes of gene expression of iron regulatory proteins during turpentine oil-induced acute-phase response in the rat

Sheikh

Dudás

Ramadori

2007

Laboratory Investigation

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Section: Discussionmentioning

confidence: 99%

Changes of gene expression of iron regulatory proteins during turpentine oil-induced acute-phase response in the rat

Sheikh

Dudás

Ramadori

2007

Laboratory Investigation

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“…Hereditary hemochromatosis is a genetic disorder associated with iron overload [1][2][3][4][5]. The tissues commonly affected in this disease are the liver, pancreas, kidney, pituitary, and heart, resulting in a myriad of diseases including liver cirrhosis, hepatocarcinoma, diabetes, cardiomyopathy, nephropathy, and endocrine dysfunction [1][2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

“…This results in the prevention of iron release from cells which express ferroportin. Duodenal enterocytes express ferroportin at the basolateral membrane, and the transporter is involved in the intestinal absorption of dietary iron [1][2][3][4][5]. Macrophages also express ferroportin and play a critical role in the recycling of heme-iron from aged erythrocytes.…”

Section: Introductionmentioning

confidence: 99%

Hepcidin expression in mouse retina and its regulation via lipopolysaccharide/Toll-like receptor-4 pathway independent of Hfe

Gnana-Prakasam

Martin

Mysona

et al. 2008

Biochemical Journal

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SummaryHepcidin is a hormone central to the regulation of iron homeostasis in the body. It is believed to be produced exclusively by the liver. Ferroportin, an iron exporter, is the receptor for hepcidin. This transporter/receptor is expressed in Müller cells, photoreceptor cells, and retinal pigment epithelium (RPE) within the retina. Since the retina is protected by the retinal-blood barriers, we asked whether ferroportin in the retina is regulated by hepcidin in the circulation or whether the retina produces hepcidin for regulation of its own iron homeostasis. Here we show that hepcidin is expressed robustly in Müller cells, photoreceptor cells, and RPE, closely resembling the expression pattern of ferroportin. We also show that bacterial lipopolysaccharide (LPS) is a regulator of hepcidin expression in Müller cells and RPE, both in vitro and in vivo, and that the regulation occurs at the transcriptional level. The action of LPS on hepcidin expression is mediated by the Toll-like receptor-4. The upregulation of hepcidin by LPS occurs independent of Hfe (Human leukocyte antigen-like protein involved in Fe homeostasis). The increase in hepcidin levels in retinal cells in response to LPS treatment is associated with a decrease in ferroportin levels. The LPS-induced upregulation of hepcidin and consequent downregulation of ferroportin is associated with increased oxidative stress and apoptosis within the retina in vivo. We conclude that retinal iron homeostasis may be regulated in an autonomous manner by hepcidin generated within the retina and that chronic bacterial infection/inflammation of the retina may disrupt iron homeostasis and retinal function.

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“…Traditionally, regulation of iron absorption has been explained by the "crypt program" [23,31]. This states that the uptake of transferrin-bound iron (TF:Fe 2 ) from the plasma by progenitor cells in the crypt of Lieberkuhn is integrated into a program that results in the inverse expression at the Fig.…”

Section: Crypt Hypothesismentioning

confidence: 99%

“…It has been hypothesized that the amount of iron acquired by the crypt cells from plasma transferrin determines the number of iron transporters produced when these cells migrate into the villus region [23] (see below). Clarification of these hypotheses will be important in determining how iron absorption is regulated, as one hypothesis predicts that hepcidin exerts its effect by altering the LIP of existing enterocytes, while the author suggests that iron acquired during crypt development modulates the transcription of the iron transport genes in enterocytes in collaboration with hepcidin.…”

mentioning

confidence: 99%

The relevance of the intestinal crypt and enterocyte in regulating iron absorption

Oates

2007

Pflugers Arch - Eur J Physiol

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Rigorous regulation of iron absorption is required to meet the requirements of the body and to limit excess iron accumulation that can produce oxidative stress. Regulation of iron absorption is controlled by hepcidin and probably by the crypt program. Hepcidin is a humoral mediator of iron absorption that interacts with the basolateral transporter, ferroportin. High levels of hepcidin reduce iron absorption by targeting ferroportin to lysosomes for destruction. It is also proposed that ferroportin is expressed on the apical membrane and coordinates with ferroportin-hepcidin derived from the basal surface to modulate the uptake phase of iron absorption. The crypt program suggests that as crypt cells differentiate and migrate into the absorptive zone they absorb iron from the diet at levels inverse to the amount of iron taken up from transferrin. Under most circumstances, intestinal iron absorption is controlled at multiple levels that lead to hepcidin/ferroportin modulation of the enterocyte labile iron pool (LIP). It is likely that transcription of iron transport proteins involved in the apical and basolateral transport of iron are differentially regulated by separate LIPs. Iron-responsive protein (IRP) 1 and IRP2 do not appear to play a significant role in the expression of iron transport proteins, although IRP2 regulates L- and H-ferritin expression. Despite the importance of hepcidin, there is evidence of hepcidin-independent regulation of iron absorption possibly involving haemojuvelin (HJV) and neogenin, which may be up-regulated during ineffective erythropoiesis.

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Iron Imports. VI. HFE and regulation of intestinal iron absorption

Cited by 40 publications

References 40 publications

Changes of gene expression of iron regulatory proteins during turpentine oil-induced acute-phase response in the rat

Changes of gene expression of iron regulatory proteins during turpentine oil-induced acute-phase response in the rat

Hepcidin expression in mouse retina and its regulation via lipopolysaccharide/Toll-like receptor-4 pathway independent of Hfe

The relevance of the intestinal crypt and enterocyte in regulating iron absorption

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