{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T08:29:55Z","timestamp":1771489795026,"version":"3.50.1"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T00:00:00Z","timestamp":1573084800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"National Health and Medical Research Council of Australia","award":["1066430"],"award-info":[{"award-number":["1066430"]}]},{"name":"National Health and Medical Research Council of Australia","award":["1043837"],"award-info":[{"award-number":["1043837"]}]},{"name":"Muscular Dystrophy Australia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Duchenne muscular dystrophy (DMD) is a lethal muscle wasting disorder caused by mutations in the DMD gene that lead to the absence or severe reduction of dystrophin protein in muscle. The mdx mouse, also dystrophin deficient, is the model most widely used to study the pathology and test potential therapies, but the phenotype is milder than human DMD. This limits the magnitude and range of histological damage parameters and molecular changes that can be measured in pre-clinical drug testing. We used three weeks of voluntary wheel running to exacerbate the mdx phenotype. In mdx mice voluntary exercise increased the amount of damaged necrotic tissue and macrophage infiltration. Global gene expression profiling revealed that exercise induced additional and larger gene expression changes in mdx mice and the pathways most impacted by exercise were all related to immune function or cell-extracellular matrix (ECM) interactions. When we compared the matrisome and inflammation genes that were dysregulated in mdx with those commonly differentially expressed in DMD, we found the exercised mdx molecular signature more closely resembled that of DMD. These gene expression changes in the exercised mdx model thus provide more scope to assess the effects of pre-clinical treatments. Our gene profiling comparisons also highlighted upregulation of extracellular matrix proteins involved in innate immunity pathways, proteases that can release them, and downstream receptors and signalling molecules in exercised mdx and DMD, suggesting that the ECM could be a major source of pro-inflammatory molecules that trigger and maintain the immune response in dystrophic muscle.<\/jats:p>","DOI":"10.1093\/hmg\/ddz266","type":"journal-article","created":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T02:51:26Z","timestamp":1573095086000},"source":"Crossref","is-referenced-by-count":12,"title":["Expression profiling in exercised mdx suggests a role for extracellular proteins in the dystrophic muscle immune response"],"prefix":"10.1093","author":[{"given":"Chantal A","family":"Coles","sequence":"first","affiliation":[{"name":"Murdoch Childrens Research Institute, Royal Children\u2019s Hospital, Melbourne, Australia"},{"name":"Faculty of Veterinary and Agricultural Science, University of Melbourne, Melbourne, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lavinia","family":"Gordon","sequence":"additional","affiliation":[{"name":"Murdoch Childrens Research Institute, Royal Children\u2019s Hospital, Melbourne, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liam C","family":"Hunt","sequence":"additional","affiliation":[{"name":"Murdoch Childrens Research Institute, Royal Children\u2019s Hospital, Melbourne, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracie","family":"Webster","sequence":"additional","affiliation":[{"name":"Agriculture Victoria, Department of Economic Development, Jobs, Transport and Resources, AgriBio, 5 Ring Rd, Bundoora, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam T","family":"Piers","sequence":"additional","affiliation":[{"name":"Murdoch Childrens Research Institute, Royal Children\u2019s Hospital, Melbourne, Australia"},{"name":"Faculty of Veterinary and Agricultural Science, University of Melbourne, Melbourne, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Kintakas","sequence":"additional","affiliation":[{"name":"Murdoch Childrens Research Institute, Royal Children\u2019s Hospital, Melbourne, Australia"},{"name":"School of Medicine and Molecular and Medical Research SRC, Deakin University, Geelong, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keryn","family":"Woodman","sequence":"additional","affiliation":[{"name":"Murdoch Childrens Research Institute, Royal Children\u2019s Hospital, Melbourne, Australia"},{"name":"Faculty of Veterinary and Agricultural Science, University of Melbourne, Melbourne, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su L","family":"Touslon","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary and Agricultural Science, University of Melbourne, Melbourne, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gayle M","family":"Smythe","sequence":"additional","affiliation":[{"name":"School of Community Health and Centre for Inland Health, Charles Sturt University, Albury-Wodonga, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason D","family":"White","sequence":"additional","affiliation":[{"name":"Murdoch Childrens Research Institute, Royal Children\u2019s Hospital, Melbourne, Australia"},{"name":"Faculty of Veterinary and Agricultural Science, University of Melbourne, Melbourne, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shireen R","family":"Lamand\u00e9","sequence":"additional","affiliation":[{"name":"Murdoch Childrens Research Institute, Royal Children\u2019s Hospital, Melbourne, Australia"},{"name":"Department of Paediatrics, University of Melbourne, Melbourne, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,11,7]]},"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/hmg\/advance-article-pdf\/doi\/10.1093\/hmg\/ddz266\/30455864\/ddz266.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/hmg\/advance-article-pdf\/doi\/10.1093\/hmg\/ddz266\/30455864\/ddz266.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T02:51:28Z","timestamp":1573095088000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/advance-article\/doi\/10.1093\/hmg\/ddz266\/5614192"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,7]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddz266","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,7]]},"article-number":"ddz266"}}