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Here we identified fibronectin type III domain containing 1 (FNDC1) as a previously uncharacterized myokine. In vitro studies showed that knockdown of\n                    <jats:italic>Fndc1<\/jats:italic>\n                    in myoblasts reduces myotube formation, while overexpression of\n                    <jats:italic>Fndc1<\/jats:italic>\n                    promotes myogenic differentiation. We further generated recombinant truncated mouse FNDC1 (mFNDC1), which retains reliable activity in promoting myoblast differentiation in vitro. Gain- and loss-of-function studies collectively showed that FNDC1 promotes cardiotoxin (CTX)-induced muscle regeneration in adult mice. Furthermore, recombinant FNDC1 treatment ameliorated pathological muscle phenotypes in the\n                    <jats:italic>mdx<\/jats:italic>\n                    mouse model of Duchenne muscular dystrophy. Mechanistically, FNDC1 bound to the integrin \u03b15\u03b21 and activated the downstream FAK\/PI3K\/AKT\/mTOR pathway to promote myogenic differentiation. Pharmacological inhibition of integrin \u03b15\u03b21 or of the downstream FAK\/PI3K\/AKT\/mTOR pathway abolished the pro-myogenic effect of FNDC1. Collectively, these results suggested that myokine FNDC1 might be used as a therapeutic agent to regulate myogenic differentiation and muscle regeneration for the treatment of acute and chronic muscle disease.\n                  <\/jats:p>","DOI":"10.1038\/s44318-024-00285-0","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T09:14:18Z","timestamp":1732094058000},"page":"30-53","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["FNDC1 is a myokine that promotes myogenesis and muscle regeneration"],"prefix":"10.1038","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2736-5646","authenticated-orcid":false,"given":"Rui Xin","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan Yuan","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong Rong","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia He","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao Chen","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao Peng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian Feng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Feng","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6753-4427","authenticated-orcid":false,"given":"Zhe","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang Kai","family":"Leng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De Fu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Ying","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4041-9151","authenticated-orcid":false,"given":"Bo","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1549-0746","authenticated-orcid":false,"given":"Jiang Wei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"key":"285_CR2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9972","volume":"6","author":"L Arnold","year":"2015","unstructured":"Arnold L, Perrin H, de Chanville CB, Saclier M, Hermand P, Poupel L, Guyon E, Licata F, Carpentier W, Vilar J et al (2015) CX3CR1 deficiency promotes muscle repair and regeneration by enhancing macrophage ApoE production. 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