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Chronic disease and inflammatory anemia (ACDI) and iron deficiency anemia (IDA) are the two most common anemias.
The main reason is the decreased availability of iron (red blood cell iron restriction response) and selective suppression of bone marrow red blood cell production.
These anemia events have also increased the global burden of major diseases.
Chronic disease and inflammatory anemia (ACDI) and iron deficiency anemia (IDA) are the two most common anemias.
Although a variety of new treatment strategies have been developed for ACDI, conventional therapies are still the standard of treatment for the disease.
Previous studies have shown that the key factors of red blood cell iron limitation response include the resistance of progenitor cells to erythropoietin (Epo), which is clinically reflected as a patient's adverse reaction to Epo treatment.
Therefore, the identification of clinically feasible strategies for erythrocyte iron restriction response may provide a safe alternative for the treatment of ACDI.
This study revealed the organelle response in the iron limitation of red blood cells, including the breakdown of the microtubule cytoskeleton and the destruction of the Golgi apparatus.
Researchers have found that isocitrate supplements that eliminate the iron restriction response of red blood cells can lead to the reassembly of microtubules and Golgi in iron-deficient progenitor cells.
This study revealed the organelle response in the iron limitation of red blood cells, including the breakdown of the microtubule cytoskeleton and the destruction of the Golgi apparatus.
Microtubule breakdown is associated with red blood cell iron restriction
According to the proteomic characteristics, ferritin, which is regulated by iron and isocitrate and interacts with microtubules, is evaluated as a candidate regulator.
Knockout of FTH1 (ferritin heavy chain) in iron-rich progenitor cells will cause the collapse of microtubules and block erythropoiesis.
On the contrary, under iron-limited conditions, increasing the expression of ferritin can restore red blood cell differentiation.
Further studies have shown that fumarate (a known ferritin inducer) can act synergistically with isocitrate to reverse the molecular and cellular defects in the iron-restricted response and improve the anemia phenotype in the mouse model.
Combination therapy of fumaric acid and isocitrate is effective for anemia
All in all, the results of this study found the cytoskeleton components in the iron restriction response of red blood cells and confirmed its potential for targeted therapy in ACDI.
The results of this study found the cytoskeleton components in the iron restriction response of red blood cells and confirmed its potential for targeted therapy in ACDI.
Original source:
Goldfarb, AN, Freeman, KC, Sahu, RK et al.
org/10.
1038/s41467-021-21938-2">Iron control of erythroid microtubule cytoskeleton as a potential target in treatment of iron-restricted anemia .
org/10.
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