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Blood, 26 February 2009, Vol. 113, No. 9, pp. 2108-2117. Prepublished online as a Blood First Edition Paper on December 24, 2008; DOI 10.1182/blood-2008-07-166942. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2008-07-166942v1 113/9/2108    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bonder, C. S Articles by Gamble, J. R Search for Related Content PubMed PubMed Citation Articles by Bonder, C. S Articles by Gamble, J. R Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 10, 2008 Accepted November 7, 2008 Sphingosine kinase regulates the rate of endothelial progenitor cell differentiation Claudine S Bonder*, Wai Y Sun, Tyson Matthews, Carlos Cassano, Xiaochun Li, Hayley S Ramshaw, Stuart M Pitson, Angel F Lopez, P Toby Coates, Richard L Proia, Mathew A Vadas, and Jennifer R Gamble Division of Human Immunology, Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, SA, Australia School of Medicine, University of Adelaide, Adelaide, SA, Australia Centenary Institute, Sydney, NSW, Australia Transplantation Immunology Laboratory, The Queen Elizabeth Hospital, Adelaide, SA, Australia Genetics of Development and Disease Branch, National Institutes of Health, Bethesda, MD, United States Medical Foundation, University of Sydney, Sydney, NSW, Australia * Corresponding author; email: claudine.bonder{at}imvs.sa.gov.au. Circulating endothelial progenitor cells (EPCs) are incorporated into foci of neovascularization where they undergo differentiation to mature endothelial cells (ECs). We show here that the enzyme sphingosine kinase-1 (SK-1) regulates the rate and direction of EPC differentiation without effect on the hematopoietic compartment. EPCs have high levels of SK-1 activity which diminishes with differentiation and is, at least partially, responsible for maintaining their EPC phenotype. EPCs from SK-1 knockout mice form more adherent EC units and acquire a mature EC phenotype more rapidly. Conversely, EPCs from mice over-expressing SK-1 in the EC compartment are retarded in their differentiation. Exogenous regulation of SK-1 levels in normal EPCs, by genetic and pharmacological means, including the immunomodulating drug FTY720, recapitulates these effects on EC differentiation. SK-1 knockout mice have higher levels of circulating EPCs, an exaggerated response to erythropoietin-induced EPC mobilization and in a mouse model of kidney ischemia reperfusion injury exhibit a recovery similar to that of ischemic mice administered exogenous EPCs. Thus, SK-1 is a critical player in EPC differentiation into EC pointing to the potential utility of SK-1 modifying agents in the specific manipulation of endothelial development and repair. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Hla Plugging Vascular Leak by Sphingosine Kinase From Bone Marrow Progenitor Cells Circ. Res., September 25, 2009; 105(7): 614 - 616. [Full Text] [PDF]

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