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PMID: 17403918 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Erythropoietin modulation of podocalyxin and a proposed erythroblast niche.

Blood ·Vol. 110 ·No. 2 ·2007-07-15 ·Pages 509-18

Sathyanarayana P, Menon MP, Bogacheva O, Bogachev O, Niss K, Kapelle WS, Houde E, Fang J, Wojchowski DM

Abstract

Epo's erythropoietic capacity is ascribed largely to its antiapoptotic actions. In part via gene profiling of bone marrow erythroblasts, Epo is now shown to selectively down-modulate the adhesion/migration factors chemokine receptor-4 (Cxcr4) and integrin alpha-4 (Itga4) and to up-modulate growth differentiation factor-3 (Gdf3), oncostatin-M (OncoM), and podocalyxin like-1 (PODXL). For PODXL, Epo dose-dependent expression of this CD34-related sialomucin was discovered in Kit(+)CD71(high) proerythroblasts and was sustained at subsequent Kit(-)CD71(high) and Ter119(+) stages. In vivo, Epo markedly induced PODXL expression in these progenitors and in marrow-resident reticulocytes. This was further associated with a rapid release of PODXL(+) reticulocytes to blood. As studied in erythroblasts expressing minimal Epo receptor (EpoR) alleles, efficient PODXL induction proved dependence on an EpoR-PY343 Stat5 binding site. Moreover, in mice expressing an EpoR-HM F343 allele, compromised Epo-induced PODXL expression correlated with abnormal anucleated red cell representation in marrow. By modulating this select set of cell-surface adhesion molecules and chemokines, Epo is proposed to mobilize erythroblasts from a hypothesized stromal niche and possibly promote reticulocyte egress to blood.

MeSH Terms
Animals Apoptosis/drug effects Bone Marrow Cells/cytology,drug effects,physiology Cell Nucleus/physiology Erythroblasts/drug effects,physiology Erythropoietin/pharmacology Flow Cytometry Gene Expression Profiling Mice Oligonucleotide Array Sequence Analysis Receptors, Erythropoietin/genetics Reverse Transcriptase Polymerase Chain Reaction Sialoglycoproteins/drug effects,genetics Sialomucins/drug effects,genetics
Chemicals
Receptors, Erythropoietin Sialoglycoproteins Sialomucins podocalyxin Erythropoietin
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Sathyanarayana Pradeep
Stem and Progenitor Cell Biology Program and Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME 04074, USA.
Menon Madhu P
Bogacheva Olga
Bogachev Oleg
Niss Knut
Kapelle William S
Houde Estelle
Fang Jing
Wojchowski Don M
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2006-11-056465
Published
2007-07-15
Epub
2007-00-02
Pages
509-18
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC1924484
Subset
IM
Grants
NHLBI NIH HHS · R01 HL044491 · United States
NCRR NIH HHS · P20-RR18789 · United States
NCRR NIH HHS · P20-RR15555 · United States
NCRR NIH HHS · P20 RR015555 · United States
NCRR NIH HHS · P20 RR018789 · United States
External Links
PubMed source DOI: 10.1182/blood-2006-11-056465 PMC Full Text View journal details
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