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Regulation of the chondroitin/dermatan fine structure by transforming growth factor-beta 1 through effects on polymer-modifying enzymes

Tiedemann, K; Olander, B; Eklund, Erik LU ; Todorova, Lizbet LU ; Bengtsson, Martin; Maccarana, Marco LU ; Westergren-Thorsson, Gunilla LU and Malmström, Anders LU (2005) In Glycobiology 15(12). p.1277-1285
Abstract
The chondroitin/dermatan sulfate proteoglycans (CS/DSPGs), biglycan, decorin, and versican play several important roles in extracellular matrix influencing matrix organization, cell proliferation, and recruitment. Moreover, they bind and regulate growth factors in the extracellular matrix. We have previously shown that cultured human lung fibroblasts treated with transforming growth factor-beta (TGF-beta) alone or in combination with epidermal growth factor and platelet-derived growth factor, increase the production of these PGs. In this report, we describe that the structure of their galactosaminoglycan side chains is altered, albeit there is no alteration of polysaccharide length. The findings showed that iduronic acid content is reduced... (More)
The chondroitin/dermatan sulfate proteoglycans (CS/DSPGs), biglycan, decorin, and versican play several important roles in extracellular matrix influencing matrix organization, cell proliferation, and recruitment. Moreover, they bind and regulate growth factors in the extracellular matrix. We have previously shown that cultured human lung fibroblasts treated with transforming growth factor-beta (TGF-beta) alone or in combination with epidermal growth factor and platelet-derived growth factor, increase the production of these PGs. In this report, we describe that the structure of their galactosaminoglycan side chains is altered, albeit there is no alteration of polysaccharide length. The findings showed that iduronic acid content is reduced by 50% in decorin and biglycan, whereas 4-O-sulfation is increased 2-fold in versican. To unravel the mechanism behind these changes, the activities of chondroitin C-5 epimerase and of O-sulfotransferases in cellular fractions prepared from fibroblasts were quantitated, and transcript levels of the relevant sulfotransferases were measured by real time polymerase chain reaction (RT-PCR). The C-5 epimerase activity was reduced by 25% in TGF-beta 1 treated cells and 50% in fibroblasts treated with the growth factor combination. No change in activity in dermatan 4-O sulfotransferase was observed, and only a minor decrease in dermatan 4-O-sulfotransferase-1 (D4ST-1) mRNA was observed. On the other hand, chondroitin 4-O sulfotransferase activity increased 2-fold upon TGF-beta 1 treatment and 3-fold upon treatment with the growth factor combination. This is in agreement with a 2-fold up-regulation of chondroitin-4-O-sulfotransferase 1 (C4ST-1) mRNA, and no changes in chondroitin-4-O-sulfotransferase 2 (C4ST-2) mRNA. Thus, cellular activity and transcript level correlated well with the changes in the structure of the dermatan/chondroitin sulfate chains. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
glucuronyl c5-epimerase, chondroitin, sulfotransferase, dermatan, glycosaminoglycan
in
Glycobiology
volume
15
issue
12
pages
1277 - 1285
publisher
Oxford University Press
external identifiers
  • pmid:16118286
  • wos:000233492100004
  • scopus:28444463260
ISSN
1460-2423
DOI
10.1093/glycob/cwj027
language
English
LU publication?
yes
id
6173d342-4595-465f-8803-89a37f3cc939 (old id 212240)
date added to LUP
2007-08-23 18:14:26
date last changed
2017-09-03 04:26:23
@article{6173d342-4595-465f-8803-89a37f3cc939,
  abstract     = {The chondroitin/dermatan sulfate proteoglycans (CS/DSPGs), biglycan, decorin, and versican play several important roles in extracellular matrix influencing matrix organization, cell proliferation, and recruitment. Moreover, they bind and regulate growth factors in the extracellular matrix. We have previously shown that cultured human lung fibroblasts treated with transforming growth factor-beta (TGF-beta) alone or in combination with epidermal growth factor and platelet-derived growth factor, increase the production of these PGs. In this report, we describe that the structure of their galactosaminoglycan side chains is altered, albeit there is no alteration of polysaccharide length. The findings showed that iduronic acid content is reduced by 50% in decorin and biglycan, whereas 4-O-sulfation is increased 2-fold in versican. To unravel the mechanism behind these changes, the activities of chondroitin C-5 epimerase and of O-sulfotransferases in cellular fractions prepared from fibroblasts were quantitated, and transcript levels of the relevant sulfotransferases were measured by real time polymerase chain reaction (RT-PCR). The C-5 epimerase activity was reduced by 25% in TGF-beta 1 treated cells and 50% in fibroblasts treated with the growth factor combination. No change in activity in dermatan 4-O sulfotransferase was observed, and only a minor decrease in dermatan 4-O-sulfotransferase-1 (D4ST-1) mRNA was observed. On the other hand, chondroitin 4-O sulfotransferase activity increased 2-fold upon TGF-beta 1 treatment and 3-fold upon treatment with the growth factor combination. This is in agreement with a 2-fold up-regulation of chondroitin-4-O-sulfotransferase 1 (C4ST-1) mRNA, and no changes in chondroitin-4-O-sulfotransferase 2 (C4ST-2) mRNA. Thus, cellular activity and transcript level correlated well with the changes in the structure of the dermatan/chondroitin sulfate chains.},
  author       = {Tiedemann, K and Olander, B and Eklund, Erik and Todorova, Lizbet and Bengtsson, Martin and Maccarana, Marco and Westergren-Thorsson, Gunilla and Malmström, Anders},
  issn         = {1460-2423},
  keyword      = {glucuronyl c5-epimerase,chondroitin,sulfotransferase,dermatan,glycosaminoglycan},
  language     = {eng},
  number       = {12},
  pages        = {1277--1285},
  publisher    = {Oxford University Press},
  series       = {Glycobiology},
  title        = {Regulation of the chondroitin/dermatan fine structure by transforming growth factor-beta 1 through effects on polymer-modifying enzymes},
  url          = {http://dx.doi.org/10.1093/glycob/cwj027},
  volume       = {15},
  year         = {2005},
}