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Blood, 15 September 2005, Vol. 106, No. 6, pp. 1956-1964. Prepublished online as a Blood First Edition Paper on June 9, 2005; DOI 10.1182/blood-2005-02-0657. This Article Full Text (PDF) All Versions of this Article: 2005-02-0657v1 106/6/1956    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 Pan, C. Articles by Gupta, P. Search for Related Content PubMed PubMed Citation Articles by Pan, C. Articles by Gupta, P. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 16, 2005 Accepted May 21, 2005 Functional abnormalities of heparan sulfate in mucopolysaccharidosis-I are associated with defective biological activity of FGF-2 on human multipotent progenitor cells Chendong Pan, Matthew S Nelson, Morayma Reyes, Lisa Koodie, Joseph J Brazil, Elliot J Stephenson, Robert C Zhao, Charles Peters, Scott B Selleck, Sally E Stringer, and Pankaj Gupta* Hematology/Oncology Section, Veterans Affairs Medical Center, Minneapolis, MN, USA Stem Cell Institute, University of Minnesota Medical School, Minneapolis, MN, USA Chinese Academy of Medical Sciences and State Key Laboratory of Experimental Hematology, Beijing, China Pediatric Hematology-Oncology and Blood and Marrow Transplantation Program, University of Minnesota Medical School, Minneapolis, MN, USA Dept. of Genetics, Cell Biology and Development, University of Minnesota Medical School, Minneapolis, MN, USA; Dept. of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA Dept. of Genetics, Cell Biology and Development, University of Minnesota Medical School, Minneapolis, MN, USA Hematology/Oncology Section, Veterans Affairs Medical Center, Minneapolis, MN, USA; Hematology-Oncology-Transplantation Division, Dept. of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA * Corresponding author; email: gupta013{at}umn.edu. In mucopolysaccharidosis-I (MPS-I), -L-iduronidase deficiency leads to progressive heparan and dermatan sulfate glycosaminoglycan (HS and DS GAG) accumulation. The functional consequences of these accumulated molecules are unknown. HS critically influence tissue morphogenesis by binding to and modulating the activity of several cytokines (e.g., FGFs) involved in developmental patterning. We recently isolated a Multipotent Progenitor Cell from postnatal human bone marrow, which differentiates into cells of all three embryonic lineages. The availability of Multipotent Progenitor Cells from normal volunteers and MPS-I (Hurler syndrome) patients provides a unique opportunity to directly examine the functional effects of abnormal HS on cytokine-mediated stem cell proliferation and survival. We demonstrate here that abnormally sulfated HS in Hurler Multipotent Progenitor Cells perturb critical FGF-2-FGFR1-HS interactions, resulting in defective FGF-2 induced proliferation and survival of Hurler Multipotent Progenitor Cells. Both the mitogenic and survival-promoting activities of FGF-2 were restored by substitution of Hurler HS by normal HS. This perturbation of critical HS-cytokine-receptor interactions may represent a mechanism by which accumulated HS contribute to the developmental pathophysiology of Hurler syndrome. Similar mechanisms may operate in the pathogenesis of other diseases where structurally abnormal GAGs accumulate. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. A. Khan, M. S. Nelson, C. Pan, P. M. Gaffney, and P. Gupta Endogenous heparan sulfate and heparin modulate bone morphogenetic protein-4 signaling and activity Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1387 - C1397. [Abstract] [Full Text] [PDF] S. A. Khan, M. S. Nelson, C. Pan, P. M. Gaffney, and P. Gupta Heparin and Endogenous Heparan Sulfate Modulate Bone Morphogenetic Protein-4 (BMP-4) Signaling and Activity. Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 4230 - 4230. [Abstract] [PDF] C. Ramos, M. Montano, C. Becerril, J. Cisneros-Lira, L. Barrera, V. Ruiz, A. Pardo, and M. Selman Acidic fibroblast growth factor decreases {alpha}-smooth muscle actin expression and induces apoptosis in human normal lung fibroblasts Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L871 - L879. [Abstract] [Full Text] [PDF] G. W. Yip, M. Smollich, and M. Gotte Therapeutic value of glycosaminoglycans in cancer. Mol. Cancer Ther., September 1, 2006; 5(9): 2139 - 2148. [Abstract] [Full Text] [PDF] G. Su, K. Meyer, C. D. Nandini, D. Qiao, S. Salamat, and A. Friedl Glypican-1 Is Frequently Overexpressed in Human Gliomas and Enhances FGF-2 Signaling in Glioma Cells Am. J. Pathol., June 1, 2006; 168(6): 2014 - 2026. [Abstract] [Full Text] [PDF]

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