エリトロポエチン発現と調節:既知のメカニズムと新たな洞察を組み合わせる

Hematopoietic growth factors are molecules that regulate the differentiation rate of hematopoietic stem cells (HSCs). Erythropoietin (EPO), primarily produced by the kidneys, plays a crucial role in erythrocyte production. When oxygen levels in the blood are low, EPO is released into the bloodstream, reaching the bone marrow, where it stimulates HSCs to differentiate and mature into erythrocytes, which are vital for oxygen transport.
Thrombopoietin (TPO), mainly released by the liver,...

Red blood cells  (RBCs) transport oxygen to all body tissues. These cells survive only for 120 days and then need to be replenished. Erythropoiesis is the process of RBC production. In healthy individuals, erythropoiesis ensures all tissues are amply supplied with oxygen. In addition, blood loss due to injury leads to a drop in the physiological oxygen level that will cause erythropoiesis. Any defect in erythropoiesis leads to several physiological disorders, including thalassemia, anemia,...

The cardiovascular system regulates the number of erythrocytes in the bloodstream to ensure optimal oxygen transport. It also prevents over-proliferation of these cells, which helps to maintain blood viscosity and flow rate.
Several factors influence the erythrocyte production rate, with tissue oxygen level being among the most critical. Intense exercise or high altitudes can cause tissue hypoxia, which triggers the kidneys to release more erythropoietin (EPO) into the bloodstream.
EPO then...

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...