{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:55:12Z","timestamp":1791507312101,"version":"4.3.4"},"reference-count":84,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T00:00:00Z","timestamp":1636070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007393","name":"French Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["23172"],"award-info":[{"award-number":["23172"]}],"id":[{"id":"10.13039\/100007393","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministero dell\u2019Istruzione, Universit\u00e0 e Ricerca PRIN2017","award":["2017FJSM9S"],"award-info":[{"award-number":["2017FJSM9S"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Skeletal muscle regeneration is a complex process involving crosstalk between immune cells and myogenic precursor cells, i.e., satellite cells. In this scenario, macrophage recruitment in damaged muscles is a mandatory step for tissue repair since pro-inflammatory M1 macrophages promote the activation of satellite cells, stimulating their proliferation and then, after switching into anti-inflammatory M2 macrophages, they prompt satellite cells\u2019 differentiation into myotubes and resolve inflammation. Here, we show that acid sphingomyelinase (ASMase), a key enzyme in sphingolipid metabolism, is activated after skeletal muscle injury induced in vivo by the injection of cardiotoxin. ASMase ablation shortens the early phases of skeletal muscle regeneration without affecting satellite cell behavior. Of interest, ASMase regulates the balance between M1 and M2 macrophages in the injured muscles so that the absence of the enzyme reduces inflammation. The analysis of macrophage populations indicates that these events depend on the altered polarization of M1 macrophages towards an M2 phenotype. Our results unravel a novel role of ASMase in regulating immune response during muscle regeneration\/repair and suggest ASMase as a supplemental therapeutic target in conditions of redundant inflammation that impairs muscle recovery.<\/jats:p>","DOI":"10.3390\/cells10113028","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T10:33:09Z","timestamp":1636108389000},"page":"3028","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Acid Sphingomyelinase Controls Early Phases of Skeletal Muscle Regeneration by Shaping the Macrophage Phenotype"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9677-9084","authenticated-orcid":false,"given":"Paulina","family":"Roux-Biejat","sequence":"first","affiliation":[{"name":"Department of Biomedical and Clinical Sciences \u201cLuigi Sacco\u201d (DIBIC), Universit\u00e0 degli Studi di Milano, 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Coazzoli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences \u201cLuigi Sacco\u201d (DIBIC), Universit\u00e0 degli Studi di Milano, 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6644-5828","authenticated-orcid":false,"given":"Pasquale","family":"Marrazzo","sequence":"additional","affiliation":[{"name":"Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, 47921 Rimini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6416-327X","authenticated-orcid":false,"given":"Silvia","family":"Zecchini","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences \u201cLuigi Sacco\u201d (DIBIC), Universit\u00e0 degli Studi di Milano, 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Di Renzo","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences \u201cLuigi Sacco\u201d (DIBIC), Universit\u00e0 degli Studi di Milano, 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2766-9006","authenticated-orcid":false,"given":"Cecilia","family":"Prata","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9691-4103","authenticated-orcid":false,"given":"Alessandra","family":"Napoli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences \u201cLuigi Sacco\u201d (DIBIC), Universit\u00e0 degli Studi di Milano, 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6614-665X","authenticated-orcid":false,"given":"Claudia","family":"Moscheni","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences \u201cLuigi Sacco\u201d (DIBIC), Universit\u00e0 degli Studi di Milano, 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Giovarelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences \u201cLuigi Sacco\u201d (DIBIC), Universit\u00e0 degli Studi di Milano, 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5686-0470","authenticated-orcid":false,"given":"Maria Cristina","family":"Barbalace","sequence":"additional","affiliation":[{"name":"Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, 47921 Rimini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1210-6836","authenticated-orcid":false,"given":"Elisabetta","family":"Catalani","sequence":"additional","affiliation":[{"name":"Department for Innovation in Biological, Agro-Food and Forest Systems (DIBAF), Universit\u00e0 degli Studi della Tuscia, 01100 Viterbo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8236-1197","authenticated-orcid":false,"given":"Maria Teresa","family":"Bassi","sequence":"additional","affiliation":[{"name":"Scientific Institute IRCCS \u201cEugenio Medea\u201d, 23842 Bosisio Parini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0365-7414","authenticated-orcid":false,"given":"Clara","family":"De Palma","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Universit\u00e0 degli Studi 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13395-014-0022-6","article-title":"Deficient nitric oxide signalling impairs skeletal muscle growth and performance: Involvement of mitochondrial dysregulation","volume":"4","author":"Morisi","year":"2014","journal-title":"Skelet. 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