PMID- 15947088
OWN - NLM
STAT- MEDLINE
DCOM- 20051011
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 106
IP  - 6
DP  - 2005 Sep 15
TI  - Functional abnormalities of heparan sulfate in mucopolysaccharidosis-I are 
      associated with defective biologic activity of FGF-2 on human multipotent 
      progenitor cells.
PG  - 1956-64
AB  - In mucopolysaccharidosis-I (MPS-I), alpha-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.
FAU - Pan, Chendong
AU  - Pan C
AD  - Associate Professor of Medicine, University of Minnesota Medical School, 
      Hematology/Oncology Section (111E), VA Medical Center, One Veterans Dr, 
      Minneapolis, MN 55417. gupta013@umn.edu.
FAU - Nelson, Matthew S
AU  - Nelson MS
FAU - Reyes, Morayma
AU  - Reyes M
FAU - Koodie, Lisa
AU  - Koodie L
FAU - Brazil, Joseph J
AU  - Brazil JJ
FAU - Stephenson, Elliot J
AU  - Stephenson EJ
FAU - Zhao, Robert C
AU  - Zhao RC
FAU - Peters, Charles
AU  - Peters C
FAU - Selleck, Scott B
AU  - Selleck SB
FAU - Stringer, Sally E
AU  - Stringer SE
FAU - Gupta, Pankaj
AU  - Gupta P
LA  - eng
PT  - Journal Article
DEP - 20050609
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Receptors, Fibroblast Growth Factor)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 9050-30-0 (Heparitin Sulfate)
RN  - EC 2.7.10.1 (FGFR1 protein, human)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 1)
SB  - IM
MH  - Case-Control Studies
MH  - Cell Proliferation
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Chromatography, High Pressure Liquid
MH  - Fibroblast Growth Factor 2/*metabolism
MH  - Heparitin Sulfate/*chemistry/isolation & purification/*physiology
MH  - Humans
MH  - Mucopolysaccharidosis I/etiology/*metabolism
MH  - Multipotent Stem Cells/cytology/*pathology
MH  - Receptor Protein-Tyrosine Kinases/metabolism
MH  - Receptor, Fibroblast Growth Factor, Type 1
MH  - Receptors, Fibroblast Growth Factor/metabolism
PMC - PMC1895139
EDAT- 2005/06/11 09:00
MHDA- 2005/10/12 09:00
PMCR- 2006/09/15
CRDT- 2005/06/11 09:00
PHST- 2005/06/11 09:00 [pubmed]
PHST- 2005/10/12 09:00 [medline]
PHST- 2005/06/11 09:00 [entrez]
PHST- 2006/09/15 00:00 [pmc-release]
AID - S0006-4971(20)63415-2 [pii]
AID - 01061956 [pii]
AID - 10.1182/blood-2005-02-0657 [doi]
PST - ppublish
SO  - Blood. 2005 Sep 15;106(6):1956-64. doi: 10.1182/blood-2005-02-0657. Epub 2005 Jun 
      9.