How do the kidneys and liver help adjust red blood cell production when oxygen levels change?

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The abstract presents a mechanistic overview, without specifying an experimental study design, named research methods, or a study population. Oxygen-dependent changes in erythropoietin production in the liver and kidneys form the basis of highly efficient feedback control of erythropoiesis—the production of red blood cells.

The cellular sites of erythropoietin synthesis had recently been identified as peritubular fibroblasts in the renal cortex, and hepatocytes and perisinusoidal Ito cells in the liver.

The main control of erythropoietin production occurs at the level of its messenger RNA (mRNA) and involves changes in the rate of transcription of the erythropoietin gene.

In the kidneys, changes in erythropoietin mRNA levels are predominantly caused by changes in the number of fibroblasts in which the gene is active. However, how these cells control erythropoietin gene activity remains unclear.

In hepatocytes, by contrast, several characteristics and components of the control of erythropoietin production had been identified in recent years. These include the binding of hypoxia-inducible proteins to specific regulatory elements of the erythropoietin gene.