{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T20:20:43Z","timestamp":1760300443367,"version":"3.40.5"},"reference-count":48,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T00:00:00Z","timestamp":1600992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003500","name":"UNIPDi","doi-asserted-by":"publisher","award":["PRAT2015"],"award-info":[{"award-number":["PRAT2015"]}],"id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013465","name":"French Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["21865"],"award-info":[{"award-number":["21865"]}],"id":[{"id":"10.13039\/100013465","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item>\n<jats:p><jats:bold>What is the central question of the study?<\/jats:bold><\/jats:p>\n<jats:p>What are the consequences of reducing circulating sphingosine\u20101\u2010phosphate (S1P) for muscle physiology in the murine model of Duchenne muscular dystrophy (DMD)?<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p><jats:bold>What is the main result and its importance?<\/jats:bold><\/jats:p>\n<jats:p>Reduction of the circulating S1P level in mdx mice aggravates the dystrophic phenotype, as seen by an increase in fibre atrophy, fibrosis and loss of specific force, suggesting that S1P signalling is a potential therapeutic target in DMD. Although further studies are needed, plasma S1P levels have the intriguing possibility of being used as a biomarker for disease severity, an important issue in DMD.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Sphingosine\u20101\u2010phosphate (S1P) is an important regulator of skeletal muscle properties. The dystrophin\u2010deficient mdx mouse possesses low levels of S1P (\u223c50%) compared with wild type. Increased S1P availability was demonstrated to ameliorate the dystrophic phenotype in <jats:italic>Drosophila<\/jats:italic> and in mdx mice. Here, we analysed the effects produced by further reduction of S1P availability on the mass, force and regenerative capacity of dystrophic mdx soleus. Circulating S1P was neutralized by a specific anti\u2010S1P antibody (S1P\u2010Ab) known to lower the extracellular concentration of this signalling lipid. The S1P\u2010Ab was administered intraperitoneally in adult mdx mice every 2\u00a0days for the duration of experiments. Soleus muscle properties were analysed 7 or 14\u00a0days after the first injection. The decreased availability of circulating S1P after the 14\u00a0day treatment reduced mdx soleus fibre cross\u2010sectional area (\u221216%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), an effect that was associated with an increase in markers of proteolytic (MuRF1 and atrogin\u20101) and autophagic (p62 and LC3\u2010II\/LC3\u2010I ratio) pathways. Moreover, an increase of fibrosis was also observed (+26%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Notably, the treatment also caused a reduction of specific tetanic tension (\u221229%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). The mdx soleus regenerative capacity was only slightly influenced by reduced S1P. In conclusion, neutralization of circulating S1P reduces the mass and specific force and increases fibrosis of mdx soleus muscle, thus worsening the dystrophic phenotype. The results confirm that active, functional S1P signalling might counteract the progression of soleus mdx pathology and validate the pathway as a potential therapeutic target for muscular dystrophies.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep088603","type":"journal-article","created":{"date-parts":[[2020,9,14]],"date-time":"2020-09-14T07:51:09Z","timestamp":1600069869000},"page":"1895-1906","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Reduction of circulating sphingosine\u20101\u2010phosphate worsens mdx soleus muscle dystrophic phenotype"],"prefix":"10.1113","volume":"105","author":[{"given":"Elena","family":"Germinario","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences University of Padova  Padova Italy"},{"name":"Interuniversity Institute of Myology  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