{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T04:26:54Z","timestamp":1762057614019,"version":"build-2065373602"},"reference-count":46,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T00:00:00Z","timestamp":1657238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM66954","MDA217712","TG2-01164","P50NS053672"],"award-info":[{"award-number":["GM66954","MDA217712","TG2-01164","P50NS053672"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["GM66954","MDA217712","TG2-01164","P50NS053672"],"award-info":[{"award-number":["GM66954","MDA217712","TG2-01164","P50NS053672"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007557","name":"Race MD Corporation (JDS), California Institute of Regenerative Medicine (CIRM)","doi-asserted-by":"publisher","award":["GM66954","MDA217712","TG2-01164","P50NS053672"],"award-info":[{"award-number":["GM66954","MDA217712","TG2-01164","P50NS053672"]}],"id":[{"id":"10.13039\/100007557","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["GM66954","MDA217712","TG2-01164","P50NS053672"],"award-info":[{"award-number":["GM66954","MDA217712","TG2-01164","P50NS053672"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Duchenne muscular dystrophy (DMD) is a congenital myopathy caused by mutations in the dystrophin gene. DMD pathology is marked by myositis, muscle fiber degeneration, and eventual muscle replacement by fibrosis and adipose tissue. Satellite cells (SC) are muscle stem cells critical for muscle regeneration. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that promotes SC proliferation, regulates lymphocyte trafficking, and is irreversibly degraded by sphingosine phosphate lyase (SPL). Here, we show that SPL is virtually absent in normal human and murine skeletal muscle but highly expressed in inflammatory infiltrates and degenerating fibers of dystrophic DMD muscle. In mdx mice that model DMD, high SPL expression is correlated with dysregulated S1P metabolism. Perinatal delivery of the SPL inhibitor LX2931 to mdx mice augmented muscle S1P and SC numbers, reduced leukocytes in peripheral blood and skeletal muscle, and attenuated muscle inflammation and degeneration. The effect on SC was also observed in SCID\/mdx mice that lack mature T and B lymphocytes. Transcriptional profiling in the skeletal muscles of LX2931-treated vs. control mdx mice demonstrated changes in innate and adaptive immune functions, plasma membrane interactions with the extracellular matrix (ECM), and axon guidance, a known function of SC. Our cumulative findings suggest that by raising muscle S1P and simultaneously disrupting the chemotactic gradient required for lymphocyte egress, SPL inhibition exerts a combination of muscle-intrinsic and systemic effects that are beneficial in the context of muscular dystrophy.<\/jats:p>","DOI":"10.3390\/ijms23147579","type":"journal-article","created":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T11:37:08Z","timestamp":1657280228000},"page":"7579","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Sphingosine Phosphate Lyase Is Upregulated in Duchenne Muscular Dystrophy, and Its Inhibition Early in Life Attenuates Inflammation and Dystrophy in Mdx Mice"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7301-138X","authenticated-orcid":false,"given":"Anabel S.","family":"De la Garza-Rodea","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, 550 16th Street, Box 0110, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6353-7900","authenticated-orcid":false,"given":"Steven A.","family":"Moore","sequence":"additional","affiliation":[{"name":"Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, Department of Pathology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesus","family":"Zamora-Pineda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, 550 16th Street, Box 0110, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric P.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University-State University of New York, Binghamton, NY 13902, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karishma","family":"Mistry","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, 550 16th Street, Box 0110, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashok","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, 550 16th Street, Box 0110, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan B.","family":"Strober","sequence":"additional","affiliation":[{"name":"Department of Neurology, UCSF Benioff Children\u2019s Hospital San Francisco, 550 16th Street, San Francisco, CA 94158, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piming","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, 550 16th Street, Box 0110, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung H.","family":"Suh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, 550 16th Street, Box 0110, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4894-919X","authenticated-orcid":false,"given":"Julie D.","family":"Saba","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, 550 16th Street, Box 0110, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1136\/bmj.2.363.541","article-title":"The pathology of paralysis with muscular degeneration (paralysie myosclerotique), or paralysis with apparent hypertrophy","volume":"2","author":"Duchenne","year":"1867","journal-title":"Br. 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