Biology Reference
In-Depth Information
Chapter 2
Epo and Non-hematopoietic Cells: What Do We Know?
Omolara O. Ogunshola and Anna Yu. Bogdanova
Abstract
The hematopoietic growth factor erythropoietin (Epo) circulates in plasma and controls the oxygen carrying
capacity of the blood (Fisher. Exp Biol Med (Maywood) 228:1-14, 2003). Epo is produced primarily in
the adult kidney and fetal liver and was originally believed to play a role restricted to stimulation of early
erythroid precursor proliferation, inhibition of apoptosis, and differentiation of the erythroid lineage.
Early studies showed that mice with targeted deletion of Epo or the Epo receptor (EpoR) show impaired
erythropoiesis, lack mature erythrocytes, and die in utero around embryonic day 13.5 (Wu et al. Cell
83:59-67, 1995; Lin et al. Genes Dev. 10:154-164, 1996). These animals also exhibited heart defects,
abnormal vascular development as well as increased apoptosis in the brain suggesting additional functions
for Epo signaling in normal development of the central nervous system and heart. Now, in addition to its
well-known role in erythropoiesis, a diverse array of cells have been identified that produce Epo and/or
express the Epo-R including endothelial cells, smooth muscle cells, and cells of the central nervous system
(Masuda et al. J Biol Chem. 269:19488-19493, 1994; Marti et al. Eur J Neurosci. 8:666-676, 1996;
Bernaudin et al. J Cereb Blood Flow Metab. 19:643-651, 1999; Li et al. Neurochem Res. 32:2132-2141,
2007). Endogenously produced Epo and/or expression of the EpoR gives rise to autocrine and paracrine
signaling in different organs particularly during hypoxia, toxicity, and injury conditions. Epo has been
shown to regulate a variety of cell functions such as calcium transport (Korbel et al. J Comp Physiol B.
174:121-128, 2004) neurotransmitter synthesis and cell survival (Velly et al. Pharmacol Ther. 128:445-
459 , 2010; Vogel et al. Blood. 102:2278-2284, 2003). Furthermore Epo has neurotrophic effects (Grimm
et al. Nat Med. 8:718-724, 2002; Junk et al. Proc Natl Acad Sci U S A. 99:10659-10664, 2002), can
induce an angiogenic phenotype in cultured endothelial cells, is a potent angiogenic factor in vivo (Ribatti
et al. Eur J Clin Invest. 33:891-896, 2003) and might enhance ventilation in hypoxic conditions (Soliz
et al. J Physiol. 568:559-571, 2005; Soliz et al. J Physiol. 583, 329-336, 2007). Thus multiple functions
have been identified breathing new life and exciting possibilities into what is really an old growth factor.
This review will address the function of Epo in non-hematopoietic tissues with significant emphasis on
the brain and heart.
Key words Non-hematopoietic cells, Adult kidney, Fetal liver, HIF
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