Blood and bones

Erythropoietin (EPO) is a glycoprotein that is critical for the regulation of red blood cell production. During embryonic development, Epo is mainly expressed in the fetal liver. However, as hematopoiesis switches sites from the fetal liver to the bone marrow, peritublular interstitial cells of the kidney support EPO production. Epo expression is tightly regulated by spatial, temporal and environmental cues. Clinically, the regulation of EPO is critical as overproduction of EPO results in the development of polycythemia and insufficient EPO production results in anemia. Over 3 million patients suffer from anemia as a result of insufficient renal EPO production. Currently, the use of recombinant Epo is the conventional treatment for anemia associated with chronic kidney disease. While this has revolutionized and transformed the lives of millions of patients, the use of recombinant Epo is costly, requires supervised administration and can have immunogenic side effects. Therefore, the identification of endogenous sources of EPO outside of the kidney that may be activated in adults for the treatment of renal anemia is of great therapeutic value. EPO expression is regulated by the hypoxia-inducible factor (HIF) family of transcription factors. Both HIF-1α and HIF-2α activate a cascade of genes including EPO in response to low tissue oxygenation or hypoxia. While HIF-1α and HIF-2α have overlapping and distinct tissue-specific expression patterns and target genes, stabilization of both proteins, in Blood and bones Osteoblastic HIF signaling regulates erythropoiesis