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Blood, 1 June 2005, Vol. 105, No. 11, pp. 4258-4263. Prepublished online as a Blood First Edition Paper on February 10, 2005; DOI 10.1182/blood-2004-07-2712. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-07-2712v1 105/11/4258    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Kirito, K. Articles by Kaushansky, K. Search for Related Content PubMed PubMed Citation Articles by Kirito, K. Articles by Kaushansky, K. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Thrombopoietin enhances expression of vascular endothelial growth factor (VEGF) in primitive hematopoietic cells through induction of HIF-1 Keita Kirito, Norma Fox, Norio Komatsu, and Kenneth Kaushansky From the Department of Medicine, Division of Hematology/Oncology, University of California, San Diego, CA; and Department of Hematology, University of Yamanashi, Yamanashi, Japan. Thrombopoietin (TPO), the primary regulator of thrombopoiesis, is also an important, nonredundant mediator of hematopoietic stem cell (HSC) development. For example, following transplantation, HSC expansion is approximately 15-fold more robust in normal than in Tpo-/- mice. Vascular endothelial growth factor (VEGF) also plays an important role in HSC development, where it acts in an intracellular autocrine fashion to promote cell survival. Thus, we tested the hypothesis that TPO affects the autocrine production of VEGF to account for its favorable effects on HSCs. We found that VEGF transcripts are reduced in purified sca-1+/c-kit+/Gr-1- marrow cells derived from Tpo-/- mice and that TPO induces VEGF transcripts in these primitive hematopoietic cells. Additional studies determined that TPO induces VEGF expression by increasing the level of its primary transcription factor, hypoxia-inducible factor 1 (HIF-1), by enhancing its protein stability. Moreover, VEGF expression is important for the TPO effect on primitive hematopoietic cells because blockade of the VEGF receptor with a specific inhibitor substantially blunts TPO-induced growth of single sca-1+/c-kit+/Gr-1- marrow cells in serum-free cultures. Along with previous findings that TPO affects Hox transcription factors that regulate HSC proliferation, these data contribute to our growing understanding of the mechanisms by which a hormone can influence stem cell development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Kanayasu-Toyoda, A. Ishii-Watabe, T. Suzuki, T. Oshizawa, and T. Yamaguchi A New Role of Thrombopoietin Enhancing ex Vivo Expansion of Endothelial Precursor Cells Derived from AC133-positive Cells J. Biol. Chem., November 16, 2007; 282(46): 33507 - 33514. [Abstract] [Full Text] [PDF] L. Petit-Cocault, C. Volle-Challier, M. Fleury, B. Peault, and M. Souyri Dual role of Mpl receptor during the establishment of definitive hematopoiesis Development, August 15, 2007; 134(16): 3031 - 3040. [Abstract] [Full Text] [PDF] J.-P. Levesque, I. G. Winkler, J. Hendy, B. Williams, F. Helwani, V. Barbier, B. Nowlan, and S. K. Nilsson Hematopoietic Progenitor Cell Mobilization Results in Hypoxia with Increased Hypoxia-Inducible Transcription Factor-1{alpha} and Vascular Endothelial Growth Factor A in Bone Marrow Stem Cells, August 1, 2007; 25(8): 1954 - 1965. [Abstract] [Full Text] [PDF] M. Ramanathan, G. Pinhal-Enfield, I. Hao, and S. J. Leibovich Synergistic Up-Regulation of Vascular Endothelial Growth Factor (VEGF) Expression in Macrophages by Adenosine A2A Receptor Agonists and Endotoxin Involves Transcriptional Regulation via the Hypoxia Response Element in the VEGF Promoter Mol. Biol. Cell, January 1, 2007; 18(1): 14 - 23. [Abstract] [Full Text] [PDF] K. Heo, U. Jariwala, J. Woo, Y. Zhan, K. A. Burke, L. Zhu, W. F. Anderson, and Y. Zhao Involvement of Niemann-Pick Type C2 Protein in Hematopoiesis Regulation Stem Cells, June 1, 2006; 24(6): 1549 - 1555. [Abstract] [Full Text] [PDF] K. Kaushansky Lineage-specific hematopoietic growth factors. N. Engl. J. Med., May 11, 2006; 354(19): 2034 - 2045. [Full Text] [PDF]

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