Work

Reactivation of Hepatic EPO Synthesis in Mice After PHD Loss

Year: 2010

Type: article

Abstract: The kidney controls erythropoietin production in adults, and the anemia that can accompany renal failure is a major medical problem. The liver controls erythropoietin production during fetal life but is silenced shortly after birth. Erythropoietin transcription is controlled by hypoxia-inducible factor (HIF), which is inhibited by three prolyl hydroxylases (PHD1, PHD2, and PHD3). Systemic PHD2 inactivation has been found to increase renal, but not hepatic, erythropoietin production. In contrast, we show here that simultaneous genetic inactivation of all three PHD paralogs in mice reactivates hepatic erythropoietin production and stimulates red blood synthesis, suggesting that pan-PHD inhibitory drugs might be useful for the treatment of anemia caused by chronic kidney disease.

Source: Science

DOI: 10.1126/science.1192811

Authors: Yoji Andrew Minamishima, William G. Kaelin

Institutions: Brigham and Women's Hospital, Howard Hughes Medical Institute, Dana-Farber Cancer Institute, Dana-Farber Brigham Cancer Center

Language: English

Topic: Erythropoietin and Anemia Treatment

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Howard Hughes Medical Institute, National Cancer Institute