Erythropoietin production in liver and kidneys

Oxygen-dependent changes of erythropoietin production in liver and kidneys provide the basis for a highly efficient feedback control of erythropoiesis. Peritubular fibroblasts in the renal cortex, hepatocytes and perisinusoidal Ito cells in the liver have recently been identified as the cellular sites of erythropoietin synthesis. The major control of erythropoietin production occurs at the level of its mRNA and involves changes in erythropoietin gene transcription rate. Modulation of renal erythropoietin mRNA levels is predominantly caused by changes in the number of fibroblasts in which the gene is active, but the cellular control of erythropoietin gene activity in these cells remains elusive. In hepatocytes, however, several characteristics and components of the control of erythropoietin production have been identified in recent years, including the binding of hypoxia-inducible proteins to specific regulatory elements of the erythropoietin gene.