Abstract:
:The kidney is the main physiologic source of erythropoietin (EPO) in the adult and responds to decreases in tissue oxygenation with increased EPO production. Although studies in mice with liver-specific or global gene inactivation have shown that hypoxia-inducible factor 2 (Hif-2) plays a major role in the regulation of Epo during infancy and in the adult, respectively, the contribution of renal HIF-2 signaling to systemic EPO homeostasis and the role of extrarenal HIF-2 in erythropoiesis, in the absence of kidney EPO, have not been examined directly. Here, we used Cre-loxP recombination to ablate Hif-2α in the kidney, whereas Hif-2-mediated hypoxia responses in the liver and other Epo-producing tissues remained intact. We found that the hypoxic induction of renal Epo is completely Hif-2 dependent and that, in the absence of renal Hif-2, hepatic Hif-2 takes over as the main regulator of serum Epo levels. Furthermore, we provide evidence that hepatocyte-derived Hif-2 is involved in the regulation of iron metabolism genes, supporting a role for HIF-2 in the coordination of EPO synthesis with iron homeostasis.
journal_name
Bloodjournal_title
Bloodauthors
Kapitsinou PP,Liu Q,Unger TL,Rha J,Davidoff O,Keith B,Epstein JA,Moores SL,Erickson-Miller CL,Haase VHdoi
10.1182/blood-2010-02-270322subject
Has Abstractpub_date
2010-10-21 00:00:00pages
3039-48issue
16eissn
0006-4971issn
1528-0020pii
blood-2010-02-270322journal_volume
116pub_type
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