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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4214-4222. Prepublished online as a Blood First Edition Paper on September 17, 2007; DOI 10.1182/blood-2007-01-067314. This Article Full Text (PDF) All Versions of this Article: blood-2007-01-067314v1 110/13/4214    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 Magnusson, P. U. Articles by Claesson-Welsh, L. Search for Related Content PubMed PubMed Citation Articles by Magnusson, P. U. Articles by Claesson-Welsh, L. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 11, 2007 Accepted August 12, 2007 FGFR-1 regulates angiogenesis through cytokines interleukin-4 and pleiotrophin Peetra U. Magnusson, Anna Dimberg, Sofie Mellberg, Agneta Lukinius, and Lena Claesson-Welsh* Department of Genetics and Pathology, Uppsala University, The Rudbeck Laboratory, Uppsala, Sweden * Corresponding author; email: lena.welsh{at}genpat.uu.se. The role of fibroblast growth factors (FGFs) in blood vessel formation has remained unclear. We employed differentiating stem cell cultures (embryoid bodies) and teratomas to show that FGF receptor-1 (FGFR-1) exerts a negative regulatory effect on endothelial cell function in these models. Embryoid bodies lacking expression of FGFR-1 as a result of gene targeting (Fgfr1-/-) displayed increased vascularization and a distinct, elongated vessel morphology. Teratomas derived from FGFR-1-deficient stem cells were characterized by an increased growth rate, and abundant, morphologically distinct vessels. Transmission electron microscopy of the Fgfr1-/- teratomas showed a compact and voluminous endothelium. The increased vascularization and altered endothelial cell morphology was dependent on secreted factor(s), based on the transfer of the Fgfr1-/- vascular phenotype by conditioned medium to Fgfr-1+/- embryoid bodies. Antibody and transcript arrays showed downregulation of interleukin 4 (IL-4) and upregulation of pleiotrophin in Fgfr1-/- embryoid bodies, compared to the heterozygous cultures. We used neutralizing antibodies to show that IL-4 and pleiotrophin act as negative and positive angiogenic regulators, respectively. We conclude that FGFR-1 negatively regulates endothelial cell function by altering the balance of modulatory cytokines. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Chen, R. A. Campbell, Y. Chang, M. Li, C. S. Wang, J. Li, E. Sanchez, M. Share, J. Steinberg, A. Berenson, et al. Pleiotrophin produced by multiple myeloma induces transdifferentiation of monocytes into vascular endothelial cells: a novel mechanism of tumor-induced vasculogenesis Blood, February 26, 2009; 113(9): 1992 - 2002. [Abstract] [Full Text] [PDF]

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