Regulation of hepatic transferrin, transferrin receptor and ferritin genes in human siderosis.
Although many studies have examined the regulation of transferrin, transferrin receptor and ferritin subunit gene expression in experimental systems, no molecular biological data in humans have been documented to date. In this study we simultaneously analyzed the hepatic content of transferrin, transferrin receptor and heavy and light ferritin subunit messenger RNAs in tissue samples obtained from subjects with normal iron balance and patients with primary or secondary iron overload. Steady-state levels of transferrin messenger RNA were not depressed by iron overload. On the contrary, they were increased (p less than 0.001) in patients with severe hepatic siderosis (liver iron content greater than 200 mumol/gm dry wt) as compared with the control group. This indicates that, as already suggested by our previous data in experimental siderosis, iron maintains the ability to induce transferrin gene activity even when cellular iron content is significantly increased. Transferrin receptor gene expression was found to respond in the same manner to any cause of iron-tissue load, regardless of the cause. In fact, a lower signal for transferrin receptor messenger RNA was consistently detected in iron-overloaded patients vs. control subjects, particularly in patients with thalassemia major and idiopathic hemochromatosis (p less than 0.001). Ferritin light-subunit messenger RNA accumulation was significantly increased in those patients with severe siderosis (idiopathic hemochromatosis and thalassemia major = liver iron between 200 and 600 mumol/gm dry wt). The fact that no significant change in hepatic ferritin heavy-subunit gene expression was detected in iron-loaded patients confirms preferential production of light-subunit--enriched ferritins in long-term iron overload.(ABSTRACT TRUNCATED AT 250 WORDS)
Pietrangelo
A
A
Clinica Medica III e Terapia Medica, University of Modena, Italy.
Rocchi
E
E
Ferrari
A
A
Ventura
E
E
Cairo
G
G
D005260:Female; D005293:Ferritins / Q000737:chemistry / Q000235:genetics*; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000502:physiology*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D011990:Receptors, Transferrin / Q000235:genetics*; D012806:Siderosis / Q000235:genetics*; D014168:Transferrin / Q000235:genetics*
D012333:RNA, Messenger; D011990:Receptors, Transferrin; D014168:Transferrin; D005293:Ferritins; D007501:Iron