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Antiproliferative heparan sulfate inhibiting hyaluronan and transforming growth factor-β expression in human lung fibroblast cells

Larsen, Kristoffer LU ; Malmström, Johan LU ; Tufvesson, Ellen LU ; Marko-Varga, György LU and Westergren-Thorsson, Gunilla LU (2005) In Clinical Proteomics 1(3-4). p.271-284
Abstract
The objective of this study was to examine the effects of heparan sulfate (HS) on factors involved in the remodeling of connective tissue observed in patients with fibrotic respiratory disorders such as asthma. A suitable working model is to stimulate human fetal lung fibroblasts in vitro with structurally different forms of HS. Highly sulfated and iduronic acid (IdoUA)-rich HS specifically decreased cell proliferaton, production of jyaluronan (HA), transforming growth factor (TGF)-β1, and TFF-β-induced α-smooth muscle actin but did not affect the overall proteoglycan production in the cells. These repressed factors are suggested to play a critical role in the early stages of remodeling and myofibroblast activation. Low sulfated and... (More)
The objective of this study was to examine the effects of heparan sulfate (HS) on factors involved in the remodeling of connective tissue observed in patients with fibrotic respiratory disorders such as asthma. A suitable working model is to stimulate human fetal lung fibroblasts in vitro with structurally different forms of HS. Highly sulfated and iduronic acid (IdoUA)-rich HS specifically decreased cell proliferaton, production of jyaluronan (HA), transforming growth factor (TGF)-β1, and TFF-β-induced α-smooth muscle actin but did not affect the overall proteoglycan production in the cells. These repressed factors are suggested to play a critical role in the early stages of remodeling and myofibroblast activation. Low sulfated and IdoUA-poor HS did not display any effects on these factors. Furthermore, analysis of the protein expression pattern by two-dimensional gel electrophoresis revealed a 70% increased expression of annexin II, which has previously been shown to have a high affinity for both heparin and HS. Heat-shock protein 27 and arsenite translocating factor, both involved in actin organization and polymerization, were also increased in the HS-stimulated cells. Thus, the reduced expression of HA and TGF-β1, both important in the development of fibrosis, seems to be mediated by pecific changes in protein expression of the fibroblast. The observed inhibition of cell proliferation, HA, and TGF-β1 allows speculation of highly sulfated HS as a antifibrotic candidate in the early stage of remodeling. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Annexin II, proteoglycan, cell growth, fibroblast, heparan sulfate, heat shock protein 27, hyaluronan, two-dimensional gel electrophoresis, transforming growth factor-β
in
Clinical Proteomics
volume
1
issue
3-4
pages
271 - 284
publisher
Humana Press
external identifiers
  • scopus:24644468107
ISSN
1559-0275
DOI
10.1385/CP:1:3-4:271
language
English
LU publication?
yes
id
9c8b2639-bb8f-40d6-9998-9b76937a1628 (old id 1133191)
date added to LUP
2008-06-25 11:34:33
date last changed
2017-01-01 04:33:33
@article{9c8b2639-bb8f-40d6-9998-9b76937a1628,
  abstract     = {The objective of this study was to examine the effects of heparan sulfate (HS) on factors involved in the remodeling of connective tissue observed in patients with fibrotic respiratory disorders such as asthma. A suitable working model is to stimulate human fetal lung fibroblasts in vitro with structurally different forms of HS. Highly sulfated and iduronic acid (IdoUA)-rich HS specifically decreased cell proliferaton, production of jyaluronan (HA), transforming growth factor (TGF)-β1, and TFF-β-induced α-smooth muscle actin but did not affect the overall proteoglycan production in the cells. These repressed factors are suggested to play a critical role in the early stages of remodeling and myofibroblast activation. Low sulfated and IdoUA-poor HS did not display any effects on these factors. Furthermore, analysis of the protein expression pattern by two-dimensional gel electrophoresis revealed a 70% increased expression of annexin II, which has previously been shown to have a high affinity for both heparin and HS. Heat-shock protein 27 and arsenite translocating factor, both involved in actin organization and polymerization, were also increased in the HS-stimulated cells. Thus, the reduced expression of HA and TGF-β1, both important in the development of fibrosis, seems to be mediated by pecific changes in protein expression of the fibroblast. The observed inhibition of cell proliferation, HA, and TGF-β1 allows speculation of highly sulfated HS as a antifibrotic candidate in the early stage of remodeling.},
  author       = {Larsen, Kristoffer and Malmström, Johan and Tufvesson, Ellen and Marko-Varga, György and Westergren-Thorsson, Gunilla},
  issn         = {1559-0275},
  keyword      = {Annexin II,proteoglycan,cell growth,fibroblast,heparan sulfate,heat shock protein 27,hyaluronan,two-dimensional gel electrophoresis,transforming growth factor-β},
  language     = {eng},
  number       = {3-4},
  pages        = {271--284},
  publisher    = {Humana Press},
  series       = {Clinical Proteomics},
  title        = {Antiproliferative heparan sulfate inhibiting hyaluronan and transforming growth factor-β expression in human lung fibroblast cells},
  url          = {http://dx.doi.org/10.1385/CP:1:3-4:271},
  volume       = {1},
  year         = {2005},
}