The chromatin-remodeling enzyme Smarca5 regulates erythrocyte aggregation via Keap1-Nrf2 signaling.
Elife
; 102021 10 26.
Article
in En
| MEDLINE
| ID: mdl-34698638
After an injury, cells in our blood (called red blood cells) often stick together to form clots to stop us from bleeding and prevent infection. These clots, however, can sometimes develop in veins and arteries, resulting in a condition known as thrombosis. If left untreated, these blockages can be life-threatening and lead to a heart attack or stroke. To study the physical effects of venous thrombosis and test different treatments, researchers often use animal models. In particular, the transparent embryos of zebrafish, as it easy to see how blood flows through their circulatory system. However, it is difficult to explore the underlying mechanisms that cause red blood cells to aggregate together using these models. To overcome this, Ding et al. developed a new model for venous thrombosis by deleting the gene for a protein called Smarca5. They found that red blood cells lacking this gene were more likely to clump together in the veins of zebrafish. Further experiments showed that this mutation reduced the activity of the gene for a protein called Keap1a, which suppresses the activity of Nrf2. Nrf2 switches on a number of genes involved in blood clotting, including the gene for the protein Hmox1a. Ding et al. discovered that increasing the activity of the gene that encodes the Keap1a protein, or decreasing the activity of the gene for Hmox1a, partially stopped red blood cells from sticking together in the zebrafish model. These findings suggest that the blood clots formed in the zebrafish model are due to the disrupted connection between Keap1a and Nrf2. This model could be used to screen new drugs for treating venous thrombosis. However, further experiments are still needed to see how similar the blood clots in the zebrafish are to the ones found in patients with this disease.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Zebrafish
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Signal Transduction
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Carrier Proteins
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Adenosine Triphosphatases
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Zebrafish Proteins
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Erythrocyte Aggregation
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NF-E2-Related Factor 2
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Elife
Year:
2021
Document type:
Article
Affiliation country:
Country of publication: