Alpha4beta1 Integrin and Erythropoietin Mediate Temporally Distinct Steps in Erythropoiesis: Integrins in Red Cell Development

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2007 Jun 6

PMID 17548514

Citations 46

Authors

Shawdee Eshghi

Mariette G Vogelezang

Richard O Hynes

Linda G Griffith

Harvey F Lodish

Affiliations

Soon will be listed here.

Abstract

Erythropoietin (Epo) is essential for the terminal proliferation and differentiation of erythroid progenitor cells. Fibronectin is an important part of the erythroid niche, but its precise role in erythropoiesis is unknown. By culturing fetal liver erythroid progenitors, we show that fibronectin and Epo regulate erythroid proliferation in temporally distinct steps: an early Epo-dependent phase is followed by a fibronectin-dependent phase. In each phase, Epo and fibronectin promote expansion by preventing apoptosis partly through bcl-xL. We show that alpha(4), alpha(5), and beta(1) are the principal integrins expressed on erythroid progenitors; their down-regulation during erythropoiesis parallels the loss of cell adhesion to fibronectin. Culturing erythroid progenitors on recombinant fibronectin fragments revealed that only substrates that engage alpha(4)beta(1)-integrin support normal proliferation. Collectively, these data suggest a two-phase model for growth factor and extracellular matrix regulation of erythropoiesis, with an early Epo-dependent, integrin-independent phase followed by an Epo-independent, alpha(4)beta(1)-integrin-dependent phase.

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