Intestinal expression of genes implicated in iron absorption and their regulation by hepcidin

Bergamaschi, Gaetano; Sabatino, Antonio Di; Pasini, Alessandra; Ubezio, C.; Costanzo, Filippo; Grataroli, Davide; Masotti, Michela; Alvisi, C; Corazza, Gino Roberto

doi:10.1016/j.clnu.2016.09.021

Cited by 43 publications

(29 citation statements)

References 29 publications

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“…This result was confirmed in primary cultured macrophages expressing endogenous FPN1 (Delaby, Pilard, Goncalves, Beaumont, & Canonne‐Hergaux, ). In the absorbing enterocytes, others and we have shown that the iron importer DMT1 rather than FPN1 is more sensitive to hepcidin‐induced internalization and degradation, a mechanism that should enhance the control over iron absorption (Bergamaschi et al, ; Brasse‐Lagnel et al, ; Mena, Esparza, Tapia, Valdes, & Nunez, ; Yamaji, Sharp, Ramesh, & Srai, ; Chaston et al, ; Laftah et al, ; Scheers, Almgren, & Sandberg, ).…”

Section: Introductionmentioning

confidence: 86%

Predominant role of microglia in brain iron retention in Sanfilippo syndrome, a pediatric neurodegenerative disease

Puy

Darwiche

Trudel

et al. 2018

Glia

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Neuroinflammation and iron accumulation are hallmarks of a variety of adult neurodegenerative diseases. In Sanfilippo syndrome (mucopolysaccharidosis type III, MPSIII, a pediatric neurodegenerative disease that shares some features with adult neurodegenerative diseases), the progressive accumulation of heparan sulfate oligosaccharides (HSOs) induces microglia and astrocytes to produce pro-inflammatory cytokines leading to severe neuroinflammation. The objectives of the present study were (1) to measure the local iron concentration and to assess iron metabolism in the brain of a MPSIIIB murine model and (2) to identify the brain cells involved in this accumulation. We found that iron accumulation in MPSIIIB mice primarily affected the cerebral cortex where hepcidin levels were higher than in wild-type mice, and increased with aging. This increase was correlated with low expression of ferroportin 1 (FPN1), and thus brain iron retention. Moreover, we showed in vitro that HSOs are directly responsible for the production of hepcidin and the relative decrease in FPN1 expression when added to cultures of microglia and, to a lesser extent, to cultures of astrocytes. In contrast, no significant differences were observed in neurons. Hepcidin induction results from activation of the TLR4 pathway and STAT3 signaling, and leads to iron retention within microglia. Our results show that microglia have a key role in cerebral hepcidin overexpression and thus in the brain iron accumulation observed in the MPSIIIB model.

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Section: Introductionmentioning

confidence: 86%

Predominant role of microglia in brain iron retention in Sanfilippo syndrome, a pediatric neurodegenerative disease

Puy

Darwiche

Trudel

et al. 2018

Glia

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“…In health, hepcidin levels rise with total body iron stores and protect against iron overload. Hepcidin is up-regulated in systemic inflammatory states by interleukin (IL) 6 and IL-1, and impairs absorption of oral iron via multiple mechanisms [20]. Adherence to oral iron therapy, particularly in adolescent IBD patients, is frequently suboptimal [21].…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of parenteral iron in children with inflammatory bowel disease

Papadopoulos

Patel

Korologou-Linden³

et al. 2018

Brit J Clinical Pharma

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Objectives: Iron deficiency anemia (IDA) frequently complicates inflammatory bowel disease (IBD) in children and adults. Oral iron may exacerbate gastrointestinal symptoms and absorption may be insufficient in intestinal inflammation. Even where oral iron is successful, repletion of iron stores can be unacceptably slow. Intravenous (IV) iron compounds were in the past associated with serious adverse reactions and historically were considered a last resort in children. New generation preparations have a safer profile in adults although reluctance to use them in children may persist, where safety data is lacking. We investigate the safety and efficacy of ferric carboxymaltose (FCM) and iron sucrose (IS) in children. Methods:We retrospectively identified all children with IBD who received parenteral iron over a 38 month period in a single regional referral centre. Safety, tolerability and adverse events were established by case note review. Efficacy was assessed by change in hematinic indices pre-and posttreatment.Results: 47 children (18 male; median age 14yrs, range 3-17) received a total of 104 iron infusions. 44% (21) had Crohn's disease (CD); 56% (27) ulcerative colitis (UC). 40 received FC, eight IS and one both. Three children developed mild rash post infusion which resolved quickly with chlorphenamine. Mean increase in hemoglobin (Hb) was 2.5g/dl (0.3-5.8). Iron levels increased by a mean of 8.4 g/dl (1-25), transfer in saturation by 16.2% (2-47). Transfer in decreased by 0.84 g/dl (0.3-3.4). Conclusion:New generation parenteral iron preparations are safe, well tolerated and efficacious in children with IDA and IBD.What is known: Iron deficiency anemia (IDA) is a common complication of inflammatory bowel disease (IBD) and a significant contributor to morbidity.IDA should be actively treated in IBD.Parenteral iron is effective and relatively safe in adults. What is new:The intravenous iron preparations ferric carboxymaltose (FCM) and iron sucrose (IS) are effective treatments for IDA in children with IBD. The safety profiles of FCM and IS are favourable, and similar in children to that in adults.

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“…Transcript levels usually are the main determinants of protein levels, and recent studies pointed that transcription, not translation, determines protein abundance in mammals . In fact, the effect of hepcidin on SLC40A1 and SLC11A2 mRNA are proportional to protein levels . However, another study demonstrated that SLC40A1 mRNA, but not SLC11A2 , is associated to protein, suggesting that additional posttranscriptional mechanisms, such as IRE/IRP system, were involved in the regulation of SLC11A2 protein levels.…”

Section: Discussionmentioning

confidence: 99%

“…The negative effects of hepcidin on SLC40A1 mRNA and protein levels have been largely demonstrated in mice . In addition, the negative effects of hepcidin on SLC40A1 mRNA levels have also been recently demonstrated in ex vivo human intestinal organ culture …”

Section: Discussionmentioning

confidence: 99%

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Increased Small Intestine Expression of Non‐Heme Iron Transporters in Morbidly Obese Patients With Newly Diagnosed Type 2 Diabetes

Moreno-Navarrete

Rodrı́guez

Becerril

et al. 2017

Molecular Nutrition Food Res

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Intestinal expression of genes implicated in iron absorption and their regulation by hepcidin

Cited by 43 publications

References 29 publications

Predominant role of microglia in brain iron retention in Sanfilippo syndrome, a pediatric neurodegenerative disease

Predominant role of microglia in brain iron retention in Sanfilippo syndrome, a pediatric neurodegenerative disease

Safety and efficacy of parenteral iron in children with inflammatory bowel disease

Increased Small Intestine Expression of Non‐Heme Iron Transporters in Morbidly Obese Patients With Newly Diagnosed Type 2 Diabetes

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