Biology Reference
In-Depth Information
There are perhaps many things we do not yet know that need
to be considered before being able to reliably use Epo and/or its
derivatives as therapeutic drugs in different disease paradigms. For
example what are the relative contributions of endogenous derived
Epo and EpoR compared to exogenous recombinant Epo that is
administered therapeutically? Do multiple tissue-specific Epo or
EpoR isoforms exist? Is the endogenous balance between pro- and
anti-apoptotic elements differentially altered by exogenous deriva-
tives and how? What are the side effects of using low or high doses
of Epo in terms of signaling pathways and negative outcomes? Can
the Epo/EpoR axis be targeted clinically for therapeutic interven-
tion in a cell or tissue-specific manner? What is the therapeutic
window for treatment considering the receptor may not always be
active? Is the route of administration critical to outcome? Can we
prime the tissue before treatment or stimulate endogenous Epo
production? And so on. The list is very long because we do not yet
know enough about the non-hematopoietic mechanisms of Epo/
EpoR in different tissues, or the short- and/or long-term effects of
modulating the system
As more research is performed and new therapeutic applica-
tions for Epo are explored, careful consideration of potential
adverse effects will need to be factored into the design of prospec-
tive clinical studies. Clearly to effectively harness the promise of
Epo-an old but now pleiotropic growth factor-questions such as
these need to be addressed now.
References
1. Fisher JW (2003) Erythropoietin: physiology
and pharmacology update. Exp Biol Med
(Maywood) 228:1-14
2. Wu H, Liu X, Jaenisch R, Lodish HF (1995)
Generation of committed erythroid BFU-E
and CFU-E progenitors does not require
erythropoietin or the erythropoietin receptor.
Cell 83:59-67
3. Lin CS, Lim SK, D'Agati V, Costantini F (1996)
Differential effects of an erythropoietin receptor
gene disruption on primitive and definitive
erythropoiesis. Genes Dev 10:154-164
4. Masuda S, Okano M, Yamagishi K, Nagao M,
Ueda M, Sasaki R (1994) A novel site of
erythropoietin production. Oxygen-
dependent production in cultured rat astro-
cytes. J Biol Chem 269:19488-19493
5. Marti HH, Wenger RH, Rivas LA, Straumann
U, Digicaylioglu M, Henn V, Yonekawa Y,
Bauer C, Gassmann M (1996) Erythropoietin
gene expression in human, monkey and
murine brain. Eur J Neurosci 8:666-676
6. Bernaudin M, Marti HH, Roussel S, Divoux D,
Nouvelot A, MacKenzie ET, Petit E (1999)
A potential role for erythropoietin in focal
permanent cerebral ischemia in mice. J Cereb
Blood Flow Metab 19:643-651
7. Li Y, Lu ZY, Ogle M, Wei L (2007)
Erythropoietin prevents blood brain barrier
damage induced by focal cerebral ischemia in
mice. Neurochem Res 32:2132-2141
8. Korbel S, Bittorf T, Siegl E, Kollner B (2004)
Recombinant human erythropoietin induces
proliferation and Ca(2+)-influx in specific leu-
kocyte subpopulations of rainbow trout
(Oncorhynchus mykiss) blood and head kid-
ney cells. J Comp Physiol B 174:121-128
9. Velly L, Pellegrini L, Guillet B, Bruder N,
Pisano P (2010) Erythropoietin 2nd cerebral
protection after acute injuries: a double-edged
sword? Pharmacol Ther 128:445-459
10. Vogel J, Kiessling I, Heinicke K, Stallmach T,
Ossent P, Vogel O, Aulmann M, Frietsch T,
Schmid-Schonbein H, Kuschinsky W,
Gassmann M (2003) Transgenic mice overex-
pressing erythropoietin adapt to excessive
erythrocytosis by regulating blood viscosity.
Blood 102:2278-2284
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