Recent experimental data indicate that HIF promotes erythropoiesis at multiple levels and coordinates cell type-specific hypoxia responses. These include renal and hepatic EPO synthesis, enhanced iron uptake and utilization, as well as changes in the bone marrow microenvironment that facilitate erythroid progenitor maturation and proliferation.

Circulating erythropoietin (EPO) is mainly produced by the kidneys and mediates erythrogenesis in bone marrow and nonhematopoietic cell survival. EPO is also produced in other tissues where it functions as a paracrine.

The Hypoxia Inducible Factor (HIF) pathway plays a key role in this regard. In this pathway, an enzyme, Prolyl Hydroxylase Domain protein 2 (PHD2), constitutively prolyl hydroxylates HIF-2α, thereby targeting HIF-2α for degradation by the von …

2013年8月15日 · Deregulation of EPO transcription caused by mutations in HIF pathway proteins is an important underlying cause of erythrocytosis in patients. Moreover, these mutations can also result in other pathologic conditions like tumor development.

2022年4月21日 · Hypoxia-inducible factors (HIFs) were discovered as activators of erythropoietin gene transcription in response to reduced oxygen (O 2) availability. O 2 -dependent hydroxylation of HIFs on proline and asparagine residues regulates protein stability and …

2023年7月26日 · EPO induction in the kidney, but not the liver, is essential for the therapeutic effects of HIF activators (HIF-PHIs) in renal anemia. HIF-PHIs indirectly, but not directly, suppress hepcidin production through EPO induction in the kidney.

However, erythropoiesis regulation extends beyond the well-established hypoxia-inducible factor (HIF)–EPO axis and involves processes modulated by other hypoxia pathway proteins (HPPs), including proteins involved in iron metabolism.

2018年5月8日 · Hypoxia is a major stimulus for HIF-2 α synthesis, which induces renal and hepatic EPO production, leading to increased serum EPO levels, stimulating then bone marrow erythropoiesis. This process needs a coordinated increase in intestinal iron absorption [ 18 ].

2019年9月1日 · Interactions between the mutated protein and HIF-1α or HIF-2α are impaired leading to increased expression of their target genes including EPO and vascular endothelial growth factor (VEGF). Chuvash erythrocytosis is associated with a high risk of both arterial and venous thrombosis in patients at sea level.

2007年4月2日 · Erythropoiesis is critically dependent on erythropoietin (EPO), a glycoprotein hormone that is regulated by hypoxia-inducible factor (HIF). Hepatocytes are the primary source of extrarenal EPO in the adult and express HIF-1 and HIF-2, whose roles in the hypoxic induction of EPO remain controversial.