title: Iduronic acid in chondroitin/dermatan sulfate affects directional migration of aortic smooth muscle cells.
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.
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden. barbara.bartolini@uninsubria.it
authors.forename: Barbara
authors.initials: B
authors.lastname: Bartolini
authors.forename: Martin A
authors.initials: MA
authors.lastname: Thelin
authors.forename: Lena
authors.initials: L
authors.lastname: Svensson
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Ghiselli
authors.forename: Toin H
authors.initials: TH
authors.lastname: van Kuppevelt
authors.forename: Anders
authors.initials: A
authors.lastname: Malmström
authors.forename: Marco
authors.initials: M
authors.lastname: Maccarana
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D002238:Carbohydrate Epimerases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D002809:Chondroitin Sulfates / Q000737:chemistry*; D003871:Dermatan Sulfate / Q000737:chemistry*; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D022001:Focal Adhesions; D015870:Gene Expression; D007067:Iduronic Acid / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D061251:Primary Cell Culture
chemical_list: D003871:Dermatan Sulfate; D007067:Iduronic Acid; D002809:Chondroitin Sulfates; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse; D002238:Carbohydrate Epimerases; C544542:dermatan sulfate epimerase 1, mouse