Erythropoietin: A Hormone with Multiple Functions

Abstract

Erythropoietin (EPO), the main hemopoietic hormone synthesized by the kidney as well as by the liver in fetal life, is implicated in mammalian erythropoiesis. Production and secretion of EPO and the expression of its receptor (EPO-R) are regulated by tissue oxygenation. EPO and EPO-R, expressed in several tissues, exert pleiotropic activities and have different effects on nonhemopoietic cells. EPO is a cytokine with antiapoptotic activity and plays a potential neuroprotective and cardioprotective role against ischemia. EPO is also involved in angiogenesis, neurogenesis, and the immune response. EPO can prevent metabolic alterations, neuronal and vascular degeneration, and inflammatory cell activation. Consequently, EPO may be of therapeutic use for a variety of disorders. Many tumors express EPO and/or EPO-R, but the action of EPO on tumor cells remains controversial. It has been suggested that EPO promotes the proliferation and survival of cancer cells expressing EPO-R. On the other hand, other reports have concluded that EPO-R plays no role in tumor progression. This review provides a detailed insight into the nonhemopoietic role of EPO and its mechanism(s) of action which may lead to a better understanding of its potential therapeutic value in diverse clinical settings.

Characterization of the erythropoietin/erythropoietin receptor axis in a rat model of liver damage and cholangiocarcinoma development

“…The biological effects of erythropoietin (EPO) are not only limited to the hematopoietic system, but also an increasing body of evidences has recently focused attention on a wide spectrum of functions in several non-hematopoietic organs (reviewed in Lombardero et al 2011). Indeed, the presence of EPO and its cognate receptor (EpoR) has been documented in many non-hematopoietic cell types, such as vascular endothelial cells, smooth muscle cells, cardiac myocytes, neurons and macrophages (Brines and Cerami 2012).…”

Therapeutic Efficacy of Tadalafil and Eriythropoietin in Experimental Spina Cord Injury

“…EPO has been claimed to promote axonal regeneration to increase neoangiogenesis, to inhibit apoptosis, to have anti-inflammatory effects, to have anti-ischemic effects, to decrease microglial infiltration, to inhibit scar formation, and thereby may contribute to neurological improvement. [15][16][17][18][19] Nevertheless, the exact mechanism of neuroprotection of EPO is still not certain. Even if key determinant to EPO secretion is hypoxia, EPO receptors are more sensitive to pro-inflammatory cytokines such as tumor necrosis factor-1 and interleukin-1 beta than hypoxia.…”

Combined Use of Erythropoietin and Laser Radiation in Experimental Spinal Stroke: Morphological and Functional Relationships

“…Наличие рецепторов к ЭПО на неэритроидных клетках (нейроны, кар-диомиоциты, эндотелиоциты, лейкоциты и др.) позволяет предположить новые эффекты ЭПО [2][3][4]7]. В частности, ЭПО играет большую роль в эмбриональном развитии мозга, восстановлении когнитивной функции и препятствии атрофии мозга при экспериментальном сотрясении, ауто-иммунном энцефаломиелите [70, 275].…”