{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T17:12:06Z","timestamp":1780593126233,"version":"3.54.1"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T00:00:00Z","timestamp":1650240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"\n Purpose<\/jats:title>\n \n Greater muscle fragility is thought to cause the exhaustion of the muscle stem cells during successive degeneration\/repair cycles, leading to muscle wasting and weakness in Duchenne muscular dystrophy. Chronic voluntary exercise can partially reduce the susceptibility to contraction induced-muscle damage, i.e., muscle fragility, as shown by a reduced immediate maximal force drop following lengthening contractions, in the dystrophic\n mdx<\/jats:italic>\n mice. Here, we studied the effect of Prospero-related homeobox factor 1 gene (\n Prox1)<\/jats:italic>\n transfer (overexpression) using an AAV on fragility in chronically exercised\n mdx<\/jats:italic>\n mice, because\n Prox1<\/jats:italic>\n promotes slower type fibres in healthy mice and slower fibres are less fragile in\n mdx<\/jats:italic>\n muscle.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Both\n tibialis anterior<\/jats:italic>\n muscles of the same\n mdx<\/jats:italic>\n mouse received the transfer of\n Prox1<\/jats:italic>\n and PBS and the mice performed voluntary running into a wheel during 1 month. We also performed\n Prox1<\/jats:italic>\n transfer in sedentary\n mdx<\/jats:italic>\n mice.\n In situ<\/jats:italic>\n maximal force production of the muscle in response to nerve stimulation was assessed before, during and after 10 lengthening contractions. Molecular muscle parameters were also evaluated.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Interestingly,\n Prox1<\/jats:italic>\n transfer reduced the isometric force drop following lengthening contractions in exercised\n mdx<\/jats:italic>\n mice (p < 0.05 to 0.01), but not in sedentary\n mdx<\/jats:italic>\n mice. It also increased the muscle expression of\n Myh7<\/jats:italic>\n (p < 0.001), MHC-2x (p < 0.01) and\n Trpc1<\/jats:italic>\n (p < 0.01), whereas it reduced that one of\n Myh4<\/jats:italic>\n (p < 0.001) and MHC-2b (p < 0.01) in exercised\n mdx<\/jats:italic>\n mice. Moreover,\n Prox1<\/jats:italic>\n transfer decreased the absolute maximal isometric force (p < 0.01), but not the specific maximal isometric force, before lengthening contraction in exercised (p < 0.01) and sedentary\n mdx<\/jats:italic>\n mice.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Our results indicate that Prox1 transfer increased the beneficial effect of chronic exercise on muscle fragility in\n mdx<\/jats:italic>\n mice, but reduced absolute maximal force. Thus, the potential clinical benefit of the transfer of Prox1 into exercised dystrophic muscle can merit further investigation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0254274","type":"journal-article","created":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T13:32:10Z","timestamp":1650288730000},"page":"e0254274","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["The beneficial effect of chronic muscular exercise on muscle fragility is increased by Prox1 gene transfer in dystrophic mdx muscle"],"prefix":"10.1371","volume":"17","author":[{"given":"Alexandra","family":"Monceau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9ment","family":"Delacroix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9gane","family":"Lemaitre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaelle","family":"Revet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Furling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onnik","family":"Agbulut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6050-4556","authenticated-orcid":true,"given":"Arnaud","family":"Ferry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,4,18]]},"reference":[{"issue":"1","key":"pone.0254274.ref001","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1152\/ajpendo.00095.2015","article-title":"Effects 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protein TRPC1 is correlated with the different degrees of the dystrophic phenotype in mdx mice","volume":"301","author":"CY Matsumura","year":"2011","journal-title":"Am J Physiol Cell Physiol"},{"issue":"1","key":"pone.0254274.ref041","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/2044-5040-1-32","article-title":"Transgenic overexpression of gamma-cytoplasmic actin protects against eccentric contraction-induced force loss in mdx mice","volume":"1","author":"KA Baltgalvis","year":"2011","journal-title":"Skelet Muscle"},{"issue":"5","key":"pone.0254274.ref042","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/mt.2009.322","article-title":"Combination of myostatin pathway interference and dystrophin rescue enhances tetanic and specific force in dystrophic mdx mice","volume":"18","author":"J Dumonceaux","year":"2010","journal-title":"Mol Ther"}],"container-title":["PLOS 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