Treatment of erythropoietin deficiency in mice with systemically administered siRNA.

Abstract	Anemia linked to a relative deficiency of renal erythropoietin production is a significant cause of morbidity and medical expenditures in the developed world. Recombinant erythropoietin is expensive and has been linked to excess cardiovascular events. Moreover, some patients become refractory to erythropoietin because of increased production of factors such as hepcidin. During fetal life, the liver, rather than the kidney, is the major source of erythropoietin. In the present study, we show that it is feasible to reactivate hepatic erythropoietin production and suppress hepcidin levels using systemically delivered siRNAs targeting the EglN prolyl hydroxylases specifically in the liver, leading to improved RBC production in models of anemia caused by either renal insufficiency or chronic inflammation with enhanced hepcidin production.
Authors	William Querbes, Roman L Bogorad, Javid Moslehi, Jamie Wong, Amy Y Chan, Elena Bulgakova, Satya Kuchimanchi, Akin Akinc, Kevin Fitzgerald, Victor Koteliansky, William G Kaelin Jr
Journal	Blood (Blood) Vol. 120 Issue 9 Pg. 1916-22 (Aug 30 2012) ISSN: 1528-0020 [Electronic] United States
PMID	22611156 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Antimicrobial Cationic Peptides HAMP protein, human Hamp protein, mouse Hepcidins RNA, Small Interfering Erythropoietin PHD1 protein, mouse PHD3 protein, mouse Procollagen-Proline Dioxygenase Egln1 protein, mouse Hypoxia-Inducible Factor-Proline Dioxygenases
Topics	Anemia (etiology, genetics, therapy) Animals Antimicrobial Cationic Peptides (genetics, metabolism) Base Sequence Cells, Cultured Erythropoiesis (genetics) Erythropoietin (deficiency, genetics, metabolism) Feasibility Studies Female Hepcidins Humans Hypoxia-Inducible Factor-Proline Dioxygenases Inflammation (complications) Liver (enzymology, metabolism) Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Procollagen-Proline Dioxygenase (genetics, metabolism) RNA Interference RNA, Small Interfering (genetics) Renal Insufficiency (complications)

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