Iduronic acid in chondroitin/dermatan sulfate affects directional migration of aortic smooth muscle cells
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 epimeras...
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| Veröffentlicht in: | PloS one 2013-07, Vol.8 (7), p.e66704-e66704 |
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| creator | Bartolini, Barbara Thelin, Martin A Svensson, Lena Ghiselli, Giancarlo van Kuppevelt, Toin H Malmström, Anders Maccarana, Marco |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0066704 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0066704</identifier><identifier>PMID: 23843960</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Adhesion ; Animals ; Aorta ; Aorta - cytology ; Aorta - metabolism ; Arteriosclerosis ; Atherosclerosis ; Basic Medicine ; Biology ; Cancer ; Carbohydrate Epimerases - deficiency ; Carbohydrate Epimerases - genetics ; Carbohydrate Epimerases - metabolism ; Cell Adhesion ; Cell and Molecular Biology ; Cell Movement ; Cell surface ; Cell- och molekylärbiologi ; Chemistry ; Chondroitin Sulfates - chemistry ; Dermatan Sulfate - chemistry ; Epimerase ; Extracellular matrix ; Fibroblasts ; Focal adhesion kinase ; Focal Adhesion Kinase 1 - genetics ; Focal Adhesion Kinase 1 - metabolism ; Focal Adhesions ; Gene Expression ; Genetic aspects ; Growth factors ; Iduronic Acid - chemistry ; Iduronic Acid - metabolism ; Kinases ; Laboratories ; Ligands ; Medical and Health Sciences ; Medicin och hälsovetenskap ; Medicinska och farmaceutiska grundvetenskaper ; Mice ; Mice, Knockout ; Morphology ; Muscles ; Myocytes, Smooth Muscle - cytology ; Myocytes, Smooth Muscle - metabolism ; Physiological aspects ; Primary Cell Culture ; Protein kinases ; Proteoglycans ; Rodents ; Science ; Smooth muscle ; Sulfates</subject><ispartof>PloS one, 2013-07, Vol.8 (7), p.e66704-e66704</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Bartolini et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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cytology</topic><topic>Aorta - metabolism</topic><topic>Arteriosclerosis</topic><topic>Atherosclerosis</topic><topic>Basic Medicine</topic><topic>Biology</topic><topic>Cancer</topic><topic>Carbohydrate Epimerases - deficiency</topic><topic>Carbohydrate Epimerases - genetics</topic><topic>Carbohydrate Epimerases - metabolism</topic><topic>Cell Adhesion</topic><topic>Cell and Molecular Biology</topic><topic>Cell Movement</topic><topic>Cell surface</topic><topic>Cell- och molekylärbiologi</topic><topic>Chemistry</topic><topic>Chondroitin Sulfates - chemistry</topic><topic>Dermatan Sulfate - chemistry</topic><topic>Epimerase</topic><topic>Extracellular matrix</topic><topic>Fibroblasts</topic><topic>Focal adhesion kinase</topic><topic>Focal Adhesion Kinase 1 - genetics</topic><topic>Focal Adhesion Kinase 1 - metabolism</topic><topic>Focal Adhesions</topic><topic>Gene Expression</topic><topic>Genetic aspects</topic><topic>Growth factors</topic><topic>Iduronic Acid - chemistry</topic><topic>Iduronic Acid - 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23843960</pmid><doi>10.1371/journal.pone.0066704</doi><tpages>e66704</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-07, Vol.8 (7), p.e66704-e66704 |
| issn | 1932-6203 1932-6203 |
| language | eng |
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| source | MEDLINE; Public Library of Science; Full-Text Journals in Chemistry (Open access); DOAJ Directory of Open Access Journals; PubMed Central; SWEPUB Freely available online; EZB Electronic Journals Library |
| subjects | Acids Adhesion Animals Aorta Aorta - cytology Aorta - metabolism Arteriosclerosis Atherosclerosis Basic Medicine Biology Cancer Carbohydrate Epimerases - deficiency Carbohydrate Epimerases - genetics Carbohydrate Epimerases - metabolism Cell Adhesion Cell and Molecular Biology Cell Movement Cell surface Cell- och molekylärbiologi Chemistry Chondroitin Sulfates - chemistry Dermatan Sulfate - chemistry Epimerase Extracellular matrix Fibroblasts Focal adhesion kinase Focal Adhesion Kinase 1 - genetics Focal Adhesion Kinase 1 - metabolism Focal Adhesions Gene Expression Genetic aspects Growth factors Iduronic Acid - chemistry Iduronic Acid - metabolism Kinases Laboratories Ligands Medical and Health Sciences Medicin och hälsovetenskap Medicinska och farmaceutiska grundvetenskaper Mice Mice, Knockout Morphology Muscles Myocytes, Smooth Muscle - cytology Myocytes, Smooth Muscle - metabolism Physiological aspects Primary Cell Culture Protein kinases Proteoglycans Rodents Science Smooth muscle Sulfates |
| title | Iduronic acid in chondroitin/dermatan sulfate affects directional migration of aortic smooth muscle cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-11T18%3A19%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Iduronic%20acid%20in%20chondroitin/dermatan%20sulfate%20affects%20directional%20migration%20of%20aortic%20smooth%20muscle%20cells&rft.jtitle=PloS%20one&rft.au=Bartolini,%20Barbara&rft.date=2013-07-02&rft.volume=8&rft.issue=7&rft.spage=e66704&rft.epage=e66704&rft.pages=e66704-e66704&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0066704&rft_dat=%3Cgale_plos_%3EA478444265%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1426970513&rft_id=info:pmid/23843960&rft_galeid=A478444265&rft_doaj_id=oai_doaj_org_article_39b89bd558a5473cb3e94b3572fe1aa6&rfr_iscdi=true |