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A compartmental model of iron regulation in the mouse.
J Theor Biol. 2006 Dec 21; 243(4):542-54.JT

Abstract

A simple compartmental model is developed for investigating the mechanism of iron homeostasis. In contrast to previous mathematical models of iron metabolism, the liver is included as a key site of iron regulation. Compartments for free iron in blood, diferric transferrin (Tf) in blood, hepatocytes, red blood cells, and macrophages are included, and their roles in iron regulation are explored. The function of hepcidin in regulating iron absorption is modeled through an inverse relationship between hepatocyte transferrin receptor 2 (TfR2) levels and the rate of iron export processes mediated by ferroportin (Fpn). Simulations of anemia and erythropoiesis stimulation support the idea that the iron demands of the erythroid compartment can be communicated through diferric Tf. The iron-responsive element of Fpn is found to be important for stabilizing intracellular iron stores in response to changing iron demands and allowing proper iron regulation through diferric Tf. The contribution of iron dysregulation to the pathogenesis of iron overload disorders is also investigated. It is shown that the characteristics of HFE hemochromatosis can be reproduced by increasing the setpoint of iron absorption in the duodenum to a level where the system cannot downregulate iron absorption to meet the iron excretion rate.

Authors+Show Affiliations

Department of Bioengineering, University of California, Los Angeles, CA 90095, USA.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16935308

Citation

Lao, Bert J., and Daniel T. Kamei. "A Compartmental Model of Iron Regulation in the Mouse." Journal of Theoretical Biology, vol. 243, no. 4, 2006, pp. 542-54.
Lao BJ, Kamei DT. A compartmental model of iron regulation in the mouse. J Theor Biol. 2006;243(4):542-54.
Lao, B. J., & Kamei, D. T. (2006). A compartmental model of iron regulation in the mouse. Journal of Theoretical Biology, 243(4), 542-54.
Lao BJ, Kamei DT. A Compartmental Model of Iron Regulation in the Mouse. J Theor Biol. 2006 Dec 21;243(4):542-54. PubMed PMID: 16935308.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A compartmental model of iron regulation in the mouse. AU - Lao,Bert J, AU - Kamei,Daniel T, Y1 - 2006/07/25/ PY - 2006/04/27/received PY - 2006/06/06/revised PY - 2006/06/16/accepted PY - 2006/8/29/pubmed PY - 2007/9/28/medline PY - 2006/8/29/entrez SP - 542 EP - 54 JF - Journal of theoretical biology JO - J Theor Biol VL - 243 IS - 4 N2 - A simple compartmental model is developed for investigating the mechanism of iron homeostasis. In contrast to previous mathematical models of iron metabolism, the liver is included as a key site of iron regulation. Compartments for free iron in blood, diferric transferrin (Tf) in blood, hepatocytes, red blood cells, and macrophages are included, and their roles in iron regulation are explored. The function of hepcidin in regulating iron absorption is modeled through an inverse relationship between hepatocyte transferrin receptor 2 (TfR2) levels and the rate of iron export processes mediated by ferroportin (Fpn). Simulations of anemia and erythropoiesis stimulation support the idea that the iron demands of the erythroid compartment can be communicated through diferric Tf. The iron-responsive element of Fpn is found to be important for stabilizing intracellular iron stores in response to changing iron demands and allowing proper iron regulation through diferric Tf. The contribution of iron dysregulation to the pathogenesis of iron overload disorders is also investigated. It is shown that the characteristics of HFE hemochromatosis can be reproduced by increasing the setpoint of iron absorption in the duodenum to a level where the system cannot downregulate iron absorption to meet the iron excretion rate. SN - 0022-5193 UR - https://www.unboundmedicine.com/medline/citation/16935308/A_compartmental_model_of_iron_regulation_in_the_mouse_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-5193(06)00270-0 DB - PRIME DP - Unbound Medicine ER -