Thyroid hormone receptor beta and NCOA4 regulate terminal erythrocyte differentiation
Abstract
We have long known that thyroid hormone (TH) stimulates formation of red blood cells and patients with thyroid diseases are often anemic, but the underlying molecular mechanisms are unclear. This study uses pharmacologic and genetic approaches in primary cells and animal models to demonstrate essential roles of nuclear receptor coactivator 4 (NCOA4) and TH in late erythropoiesis. We show that TH is essential for the last steps in formation of red cells in culture, and that treatment of cells with drugs that activate a particular nuclear TH receptor, TRβ, stimulates erythroid differentiation and alleviates anemic symptoms in a chronic anemia mouse model, indicating potential clinical applications. Further, we show that TRβ functions together with NCOA4 to regulate red cell formation.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 01, 2017
- Source ID
- 10.1073/pnas.1711058114
Entities
People
- Harvey F. Lodish
- Hsiang-Ying Lee
- M. Inmaculada Barrasa
- Michael G. Rosenfeld
- Qi Ma
- Randall Jeffrey Platt
- Russell R. Elmes
- Wenbo Li
- Xiaofei Gao
Organizations
- Health Resources in Action
- Leukemia & Lymphoma Society
- Massachusetts Institute of Technology
- National Heart, Lung, and Blood Institute
- United States Army Medical Research and Development Command
- University of California, San Diego
- Whitehead Institute