TGF-β inhibitors stimulate red blood cell production by enhancing self-renewal of BFU-E erythroid progenitors.

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.

• Authors: Xiaofei Gao, Hsiang-Ying Lee, Edroaldo Lummertz da Rocha, Cheng Zhang, Yi-Fen Lu, Dandan Li, Yuxiong Feng, Jideofor Ezike, Russell R Elmes, M Inmaculada Barrasa, Patrick Cahan, Hu Li, George Q Daley, Harvey F Lodish
• Journal: Blood (Blood) Vol. 128 Issue 23 Pg. 2637-2641 (12 08 2016) ISSN: 1528-0020 [Electronic] United States
• PMID: 27777239 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't)
• Copyright: © 2016 by The American Society of Hematology.

Chemical References

• Antigens, Differentiation
• Proteoglycans
• Receptors, Transforming Growth Factor beta
• Transforming Growth Factor beta
• Erythropoietin
• betaglycan

Topics

• Anemia (metabolism, therapy)
• Animals
• Antigens, Differentiation (metabolism)
• Erythrocytes (cytology, metabolism)
• Erythroid Precursor Cells (cytology, metabolism)
• Erythropoietin (metabolism)
• Humans
• Mice
• Proteoglycans (metabolism)
• Receptors, Transforming Growth Factor beta (metabolism)
• Signal Transduction (physiology)
• Transforming Growth Factor beta (metabolism)