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Ferroportin1 in hepatocytes and macrophages mediates systemic iron homeostasis
Author(s) -
Zhang Zhuzhen,
Zhang Fan,
Guo Xin,
An Peng,
Tao Yunlong,
Wang Fudi
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.641.17
Subject(s) - erythropoiesis , ineffective erythropoiesis , anemia , hemoglobin , hepatocyte , iron deficiency , chemistry , homeostasis , medicine , endocrinology , biology , biochemistry , in vitro
The liver is a major site for iron storage, but hepatocyte iron efflux mechanisms are unclear. To examine the hypothesis that Ferroportin1 (Fpn1) is a critical iron exporter in hepatocytes and macrophages, we generated both hepatocyte‐specific Fpn1 deletion mice ( Fpn1 Alb/Alb ), and mice that lacked Fpn1 in hepatocytes and macrophages ( Fpn1 Alb/Alb;LysM/LysM ). When fed a standard diet, Fpn1 Alb/Alb mice showed mild hepatocyte iron retention. However, RBC and hemoglobin levels were normal, indicating intact erythropoiesis. When fed an iron‐deficient diet, Fpn1 Alb/Alb mice showed impaired liver iron mobilization and anemia, with much lower RBC and hemoglobin, indicating that erythropoiesis depended upon both iron storage and iron demand status. Thus Fpn1 is critical for hepatocyte iron release. On standard diet, Fpn1 Alb/Alb;LysM/LysM mice displayed substantially increased iron retention with intact erythropoiesis implying compensatory intestinal iron absorption. When fed an iron‐deficient diet, as iron mobilization from hepatocytes and iron recycling from macrophages were impaired, Fpn1 Alb/Alb;LysM/LysM mice showed severe iron‐deficiency anemia regardless of their iron store status. Our data reveal new insights into the relationship among Fpn1‐mediated iron mobilization, iron storage, and iron absorption as these factors interact to maintain systemic iron homeostasis. Grant Funding Source : MOST of China (#2009CB941400, 2011CB966200); NSFC of China (# 10979071, 30970665, 31030039)