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Type: Journal article
Title: Sphingosine kinase regulates the rate of endothelial progenitor cell differentiation
Author: Bonder, C.
Sun, W.
Matthews, T.
Cassano, C.
Li, X.
Ramshaw, H.
Pitson, S.
Lopez, A.
Coates, P.
Proia, R.
Vadas, M.
Gamble, J.
Citation: Blood, 2009; 113(9):2108-2117
Publisher: Amer Soc Hematology
Issue Date: 2009
ISSN: 0006-4971
Statement of
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
Abstract: 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 overexpressing SK-1 in the EC compartment are retarded in their differentiation. Exogenous regulation of SK-1 levels in normal EPCs, by genetic and pharmacologic 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.
Keywords: Bone Marrow Cells; Cells, Cultured; Endothelial Cells; Stem Cells; Animals; Mice, Knockout; Mice; Serine Endopeptidases; Proprotein Convertases; Phosphotransferases (Alcohol Group Acceptor); Colony-Forming Units Assay; Cell Differentiation; Cell Proliferation; Phenotype
RMID: 0020090262
DOI: 10.1182/blood-2008-07-166942
Appears in Collections:Medicine publications

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