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Iduronic Acid in chondroitin/dermatan sulfate affects directional migration of aortic smooth muscle cells.

Bartolini, Barbara LU ; Thelin, Martin LU ; Svensson, Lena M LU ; Ghiselli, Giancarlo ; van Kuppevelt, Toin H ; Malmström, Anders LU orcid and Maccarana, Marco LU (2013) In PLoS ONE 8(7).
Abstract
Aortic smooth muscle cells produce chondroitin/dermatan sulfate (CS/DS) proteoglycans that regulate extracellular matrix organization and cell behavior in normal and pathological conditions. A unique feature of CS/DS proteoglycans is the presence of iduronic acid (IdoA), catalyzed by two DS epimerases. Functional ablation of DS-epi1, the main epimerase in these cells, resulted in a major reduction of IdoA both on cell surface and in secreted CS/DS proteoglycans. Downregulation of IdoA led to delayed ability to re-populate wounded areas due to loss of directional persistence of migration. DS-epi1-/- aortic smooth muscle cells, however, had not lost the general property of migration showing even increased speed of movement compared to wild... (More)
Aortic smooth muscle cells produce chondroitin/dermatan sulfate (CS/DS) proteoglycans that regulate extracellular matrix organization and cell behavior in normal and pathological conditions. A unique feature of CS/DS proteoglycans is the presence of iduronic acid (IdoA), catalyzed by two DS epimerases. Functional ablation of DS-epi1, the main epimerase in these cells, resulted in a major reduction of IdoA both on cell surface and in secreted CS/DS proteoglycans. Downregulation of IdoA led to delayed ability to re-populate wounded areas due to loss of directional persistence of migration. DS-epi1-/- aortic smooth muscle cells, however, had not lost the general property of migration showing even increased speed of movement compared to wild type cells. Where the cell membrane adheres to the substratum, stress fibers were denser whereas focal adhesion sites were fewer. Total cellular expression of focal adhesion kinase (FAK) and phospho-FAK (pFAK) was decreased in mutant cells compared to control cells. As many pathological conditions are dependent on migration, modulation of IdoA content may point to therapeutic strategies for diseases such as cancer and atherosclerosis. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
8
issue
7
article number
e66704
publisher
Public Library of Science (PLoS)
external identifiers
  • wos:000321341000017
  • pmid:23843960
  • scopus:84879761043
  • pmid:23843960
ISSN
1932-6203
DOI
10.1371/journal.pone.0066704
language
English
LU publication?
yes
id
e8f75a3e-fb96-49a1-82b4-df8e80c1eefa (old id 3955976)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23843960?dopt=Abstract
date added to LUP
2016-04-01 13:29:14
date last changed
2022-03-21 18:51:41
@article{e8f75a3e-fb96-49a1-82b4-df8e80c1eefa,
  abstract     = {{Aortic smooth muscle cells produce chondroitin/dermatan sulfate (CS/DS) proteoglycans that regulate extracellular matrix organization and cell behavior in normal and pathological conditions. A unique feature of CS/DS proteoglycans is the presence of iduronic acid (IdoA), catalyzed by two DS epimerases. Functional ablation of DS-epi1, the main epimerase in these cells, resulted in a major reduction of IdoA both on cell surface and in secreted CS/DS proteoglycans. Downregulation of IdoA led to delayed ability to re-populate wounded areas due to loss of directional persistence of migration. DS-epi1-/- aortic smooth muscle cells, however, had not lost the general property of migration showing even increased speed of movement compared to wild type cells. Where the cell membrane adheres to the substratum, stress fibers were denser whereas focal adhesion sites were fewer. Total cellular expression of focal adhesion kinase (FAK) and phospho-FAK (pFAK) was decreased in mutant cells compared to control cells. As many pathological conditions are dependent on migration, modulation of IdoA content may point to therapeutic strategies for diseases such as cancer and atherosclerosis.}},
  author       = {{Bartolini, Barbara and Thelin, Martin and Svensson, Lena M and Ghiselli, Giancarlo and van Kuppevelt, Toin H and Malmström, Anders and Maccarana, Marco}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  number       = {{7}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Iduronic Acid in chondroitin/dermatan sulfate affects directional migration of aortic smooth muscle cells.}},
  url          = {{https://lup.lub.lu.se/search/files/3400123/4146189}},
  doi          = {{10.1371/journal.pone.0066704}},
  volume       = {{8}},
  year         = {{2013}},
}