The role of erythropoietin in regulating angiogenesis.
Erythropoietin (EPO) is an essential growth factor that regulates erythrocyte production in mammals. In this study, we demonstrate a novel role of EPO in regulating angiogenesis in vivo. Epo and Epo receptor (EpoR) are expressed in the vasculature during embryogenesis. Deletion of Epo or EpoR leads to angiogenic defects starting at E10.5, 2 days before ventricular hypoplasia and 3 days before the onset of the embryonic lethal phenotype. Overall, angiogenesis was severely affected in the mutant embryos: vascular anomalies included decreased complexity of the vessel networks. However, de novo vasculogenesis remained intact, consistent with the differential expression of Epo and EpoR during the early stages of embryonic development. The aforementioned angiogenesis defect can be partially rescued by expressing human EPO during embryogenesis. Moreover, Ang-1 expression is regulated by EPO/EPOR under normoxic conditions. Taken together, our results suggest important roles of EPO and EPOR in angiogenesis.
Kertesz
Nathalie
N
Howard Hughes Medical Institute and Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA, 90095-1735, USA.
Wu
Jun
J
Chen
Tim H-P
TH
Sucov
Henry M
HM
Wu
Hong
H
D042683:Angiopoietin-1 / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004730:Endothelium, Vascular / Q000378:metabolism; D004921:Erythropoietin / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D017467:Receptors, Erythropoietin / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042683:Angiopoietin-1; D017467:Receptors, Erythropoietin; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin