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TGF-β inhibitors stimulate red blood cell production by enhancing self-renewal of BFU-E erythroid progenitors.
- Source :
-
Blood [Blood] 2016 Dec 08; Vol. 128 (23), pp. 2637-2641. Date of Electronic Publication: 2016 Oct 24. - Publication Year :
- 2016
-
Abstract
- Burst-forming unit erythroid progenitors (BFU-Es) are so named based on their ability to generate in methylcellulose culture large colonies of erythroid cells that consist of "bursts" of smaller erythroid colonies derived from the later colony-forming unit erythroid progenitor erythropoietin (Epo)-dependent progenitors. "Early" BFU-E cells forming large BFU-E colonies presumably have higher capacities for self-renewal than do "late" BFU-Es forming small colonies, but the mechanism underlying this heterogeneity remains unknown. We show that the type III transforming growth factor β (TGF-β) receptor (TβRIII) is a marker that distinguishes early and late BFU-Es. Transient elevation of TβRIII expression promotes TGF-β signaling during the early BFU-E to late BFU-E transition. Blocking TGF-β signaling using a receptor kinase inhibitor increases early BFU-E cell self-renewal and total erythroblast production, suggesting the usefulness of this type of drug in treating Epo-unresponsive anemias.<br /> (© 2016 by The American Society of Hematology.)
- Subjects :
- Anemia metabolism
Anemia therapy
Animals
Erythrocytes cytology
Erythroid Precursor Cells cytology
Erythropoietin metabolism
Humans
Mice
Antigens, Differentiation metabolism
Erythrocytes metabolism
Erythroid Precursor Cells metabolism
Proteoglycans metabolism
Receptors, Transforming Growth Factor beta metabolism
Signal Transduction physiology
Transforming Growth Factor beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 128
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 27777239
- Full Text :
- https://doi.org/10.1182/blood-2016-05-718320