Erythropoietin, EPO is a glycoprotein hormone secreted by the kidneys and is the “commander-in-chief” of red blood cell production in the body. Its core task is to stimulate the production of red blood cells by bone marrow hematopoietic stem cells, which act as a “refuelling” agent for the body and ensure the efficient functioning of the oxygen transport system.
 
Hypoxia is the starting signal of EPO: when the human body is in the state of the plateau, anaemia or blood loss, the kidneys sense the lack of oxygen and immediately release EPO, which sends the instruction of “accelerating the production of red blood cells” to the bone marrow.

Medical value: Artificial recombinant EPO is a “golden drug” for the treatment of renal anaemia and post-chemotherapy anaemia.
Areas of controversy: EPO has been abused in sports (e.g. endurance sports) for its ability to enhance the oxygen-carrying capacity of the blood.
 

Erythropoietin 01

Biochemical Basis of EPO: Structure Determines Function
 
Molecular Structure and Characterization
Multistage Structure
Primary structure: a single chain polypeptide of 165 amino acids containing three N-linked glycosylation sites (Asn24, Asn38, Asn83) and one O-linked glycosylation site (Ser126).
Three-dimensional conformation: 4 α-helices (A-D) with 2 long loops (AB, CD loops) form a spherical structure in which the C-helix binds specifically to the D1 structural domain of the EPO receptor (EPOR).

Glycosylation Modification Effects
Stability: sialylated glycan chains extend plasma half-life (10-fold faster clearance after deglycosylation).
Bioactivity: core fucoidan glycosylation may affect receptor binding efficiency.
Gene Expression Regulation
Chromosomal localization: The human EPO gene is located at 7q21-22 and contains 5 exons.
Hypoxia response element (HRE): HRE (5'-RCGTG-3') in the EPO promoter is the binding site for the HIF-1α/ARNT heterodimer, which drives transcriptional activation under hypoxic conditions.
Epistatic regulation: histone deacetylase (HDAC) inhibitors enhance EPO expression, suggesting a regulatory role for histone acetylation status.
 

Erythropoietin 02

EPO-EPOR Signaling Pathway
EPO initiates the classical JAK/STAT signaling cascade by binding to the cell-surface EPO receptor (EPOR), while triggering a multi-pathway cross-regulatory network:

Key Steps in Receptor Activation
EPOR conformational changes: EPO binding induces EPOR dimerization, narrowing of the intracellular structural domain spacing (bonding model shows a shortening of the distance from 73 Å to 39 Å) and activation of the JAK2 kinase structural domain.
Key phosphorylation events:
①JAK2 autophosphorylation (Tyr1007/1008) → STAT5 recruitment and phosphorylation → formation of STAT5 dimer into the nucleus to regulate target genes (e.g. Bcl-2, Cyclin D1).
② RAS/MAPK pathway: proliferative signaling through Gab1 and SHC adaptor protein.
③ PI3K/Akt pathway: inhibits FoxO3a-mediated pro-apoptotic gene expression.

Negative Feedback Regulatory Mechanism
SOCS protein family: EPO induces SOCS3 expression, competitively binds EPOR phosphorylation sites, and inhibits JAK2 activity.
Receptor ubiquitination degradation: Cbl family E3 ubiquitin ligase tags the EPOR complex and down-regulates signal intensity via the proteasome pathway.

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Core Scientific Model for EPO Research
Classical Cell Model
Mouse erythroleukemia cells (MEL): can be induced to differentiate into hemoglobin-synthesizing cells, used to study the regulation of red lineage differentiation by EPO.
Human leukemia cell line (UT-7/EPO): EPO-dependent cells, commonly used for drug sensitivity testing.
Primary culture model: mouse fetal liver erythroid progenitor cells (CFU-E) in vitro colony formation assay to assess EPO bioactivity.

Animal Model
EPO transgenic mice: overexpression of EPO leads to erythrocytosis and mimics the plateau acclimatization response.
EPOR knockout mice: embryonic lethality due to severe anemia, to verify the necessity of EPO in development.
5/6 nephrectomy model: simulating anaemia in chronic kidney disease for rhEPO efficacy evaluation.  

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EPO Frontier Research Directions and Challenges
New Perception of Non-classical Function
Neuroprotective effects: EPO can cross the blood-brain barrier and activate the PI3K/Akt pathway to reduce neuronal apoptosis after ischemic stroke.
Tumor pro-survival controversy: some solid tumors (e.g., breast cancer) promote angiogenesis through paracrine EPO, but whether the mechanism is dependent on EPOR remains questionable.

Bioengineering Modification
Long-lasting rhEPO development: polyethene glycol (PEG)-modified or Fc fusion proteins (e.g., Darbepoetin alfa) to extend half-life.
Gene therapy attempts: AAV vector delivery of EPO gene for renal anaemia.
 
As the “soul hormone” of erythropoiesis, the detection of EPO is of great significance for disease diagnosis and scientific research. Whether it is to explore the mystery of plateau adaptation or to optimize the treatment of anaemia, high-sensitivity ELISA kits are your reliable partners.
 
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Jonlnbio Citations
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JL12771  Mouse Erythropoietin (EPO)ELISA Kit

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Article: Biogenic Selenium Nanoparticles Synthesized by Lactobacillus casei ATCC 393 Alleviate Acute Hypobaric Hypoxia-Induced Intestinal Barrier Dysfunction in C57BL/6 Mice.
Cited Products:
JL20316  Mouse Hypoxia Inducible Factor 1 Alpha (HIF-1α)ELISA Kit
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JL12771  Mouse Erythropoietin (EPO)ELISA Kit
JL11855  Mouse Diamine Oxidase(DAO)ELISA Kit
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