Iduronic Acid in chondroitin/dermatan sulfate affects directional migration of aortic smooth muscle cells.
Author
Summary, in English
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.
Department/s
- Matrix Biology
- Department of Experimental Medical Science
Publishing year
2013
Language
English
Publication/Series
PLoS ONE
Volume
8
Issue
7
Full text
Links
Document type
Journal article
Publisher
Public Library of Science (PLoS)
Topic
- Cell and Molecular Biology
- Basic Medicine
Status
Published
Research group
- Matrix Biology
ISBN/ISSN/Other
- ISSN: 1932-6203