Background and aims: While upregulation of divalent metal transporter 1 (DMT1) and iron regulated gene 1 (IREG1)within duodenal enterocytes is reported in patients with hereditary haemochromatosis (HH), these findings...Background and aims: While upregulation of divalent metal transporter 1 (DMT1) and iron regulated gene 1 (IREG1)within duodenal enterocytes is reported in patients with hereditary haemochromatosis (HH), these findings are controversial. Furthermore,the effect of HFE, the gene mutated in HH, on expression of these molecules is unclear. This study examines duodenal expression of these three molecules in HH patients(prior to and following phlebotomy), in patients with iron deficiency (ID), and in controls. Methods: DMT1, IREG1, and HFE mRNA were measured in duodenal tissue of C282Y homozygous HH patients, in ID patients negative for the C282Y mutation with a serum ferritin concentration less than 20 μ g/l,and in controls negative for C282Y and H63D mutations with normal iron indices, using real time polymerase chain reaction.Resells: DMT1 and IREG1 mRNA levels were not significantly different in non-phlebotomised (untreated) HH patients compared with controls. DMT1 expression was significantly increased in HH patients who had undergone phlebotomy therapy(treated) and in patients with ID compared with controls.IREG1 was significantly increased in ID patients relative to controls, and while IREG1 expression was 1.8-fold greater in treated HH patients, this was not statistically significant.HFE mRNA expression was not significantly different in any of the groups investigated relative to controls. Conclusions:These findings demonstrate that untreated HH patients do not have increased duodenal DMT1 and IREG mRNA, but rather phlebotomy increases expression of these molecules, reflecting the effect of phlebotomy induced erythropoiesis. Finally, HFE appears to play a minor role in the regulation of iron absorption by the duodenal enterocyte.展开更多
Iron is an essential trace metal in the human diet due to its obligate role in a number of metabolic processes. In the diet, iron is present in a number of different forms, generally described as haem （from haemoglob...Iron is an essential trace metal in the human diet due to its obligate role in a number of metabolic processes. In the diet, iron is present in a number of different forms, generally described as haem （from haemoglobin and myoglobin in animal tissue） and non-haem iron （including ferric oxides and salts, ferritin and lactoferrin）. This review describes the molecular mechanisms that co-ordinate the absorption of iron from the diet and its release into the circulation. While many components of the iron transport pathway have been elucidated, a number of key issues still remain to be resolved. Future work in this area will provide a clearer picture regarding the transcellular flux of iron and its regulation by dietary and humoral factors.展开更多
文摘Background and aims: While upregulation of divalent metal transporter 1 (DMT1) and iron regulated gene 1 (IREG1)within duodenal enterocytes is reported in patients with hereditary haemochromatosis (HH), these findings are controversial. Furthermore,the effect of HFE, the gene mutated in HH, on expression of these molecules is unclear. This study examines duodenal expression of these three molecules in HH patients(prior to and following phlebotomy), in patients with iron deficiency (ID), and in controls. Methods: DMT1, IREG1, and HFE mRNA were measured in duodenal tissue of C282Y homozygous HH patients, in ID patients negative for the C282Y mutation with a serum ferritin concentration less than 20 μ g/l,and in controls negative for C282Y and H63D mutations with normal iron indices, using real time polymerase chain reaction.Resells: DMT1 and IREG1 mRNA levels were not significantly different in non-phlebotomised (untreated) HH patients compared with controls. DMT1 expression was significantly increased in HH patients who had undergone phlebotomy therapy(treated) and in patients with ID compared with controls.IREG1 was significantly increased in ID patients relative to controls, and while IREG1 expression was 1.8-fold greater in treated HH patients, this was not statistically significant.HFE mRNA expression was not significantly different in any of the groups investigated relative to controls. Conclusions:These findings demonstrate that untreated HH patients do not have increased duodenal DMT1 and IREG mRNA, but rather phlebotomy increases expression of these molecules, reflecting the effect of phlebotomy induced erythropoiesis. Finally, HFE appears to play a minor role in the regulation of iron absorption by the duodenal enterocyte.
文摘Iron is an essential trace metal in the human diet due to its obligate role in a number of metabolic processes. In the diet, iron is present in a number of different forms, generally described as haem （from haemoglobin and myoglobin in animal tissue） and non-haem iron （including ferric oxides and salts, ferritin and lactoferrin）. This review describes the molecular mechanisms that co-ordinate the absorption of iron from the diet and its release into the circulation. While many components of the iron transport pathway have been elucidated, a number of key issues still remain to be resolved. Future work in this area will provide a clearer picture regarding the transcellular flux of iron and its regulation by dietary and humoral factors.
