|
|
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.
 Previous Article | Table of Contents | Next Article 
HEMATOPOIESIS
Functional abnormalities of heparan sulfate in mucopolysaccharidosis-I are associated with defective biologic 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
From the Hematology/Oncology Section, Veterans Affairs Medical Center; the Stem Cell Institute, the Pediatric Hematology-Oncology and Blood and Marrow Transplantation Program, the Department of Genetics, Cell Biology and Development, the Department of Pediatrics, and the Hematology-Oncology-Transplantation Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN; and the Chinese Academy of Medical Sciences and State Key Laboratory of Experimental Hematology, Beijing, China.
In mucopolysaccharidosis-I (MPS-I),  -L-iduronidase deficiency leads to progressive heparan sulfate (HS) and dermatan sulfate (DS) glycosaminoglycan (GAG) accumulation. The functional consequences of these accumulated molecules are unknown. HS critically influences tissue morphogenesis by binding to and modulating the activity of several cytokines (eg, fibroblast growth factors [FGFs]) involved in developmental patterning. We recently isolated a multipotent progenitor cell from postnatal human bone marrow, which differentiates into cells of all 3 embryonic lineages. The availability of multipotent progenitor cells from healthy volunteers and patients with MPS-I (Hurler syndrome) 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 contributes 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]
|
|
|
| |
