EPOsecreting

EPOsecreting refers to cells that synthesize and release erythropoietin (EPO), a glycoprotein hormone essential for the regulation of red blood cell production. In mammals, the primary sources are the kidneys, where renal interstitial fibroblasts in the cortex and outer medulla produce most EPO in response to hypoxia. During fetal development, the liver is the major source of EPO; after birth, hepatic production diminishes but can contribute under certain conditions.

Cell types involved in EPO secretion include the renal peritubular interstitial fibroblasts, which respond to low oxygen levels by increasing EPO transcription. In addition, a small population of hepatic, and potentially extrarenal, cells can contribute to EPO production under hypoxic stress or disease. Extrarenal EPO production has been observed in various tissues, including adipose tissue and certain tumors, particularly in pathological or severely hypoxic states.

Regulation of EPO secretion is tightly linked to oxygen sensing. Hypoxia-inducible factors (mostly HIF-2α) drive transcription of the EPO gene. Under normoxic conditions, prolyl hydroxylases mark HIF-α for degradation via the VHL E3 ubiquitin ligase complex, reducing EPO production. Hypoxia stabilizes HIF-2α, upregulating EPO synthesis. Iron status, inflammatory signals, and other metabolic cues can influence the magnitude of EPO expression.

Physiological role and clinical relevance: EPO acts on erythroid progenitors in the bone marrow through the EPO receptor, activating signaling pathways such as JAK2-STAT5 to promote cell survival, proliferation, and maturation, thereby increasing red cell mass and oxygen delivery. Clinically, reduced renal EPO production contributes to anemia in chronic kidney disease, while EPO-secreting tumors can cause secondary polycythemia. Recombinant EPO is used therapeutically to treat various forms of anemia.