{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T07:05:30Z","timestamp":1766387130332,"version":"3.48.0"},"reference-count":55,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870363"],"award-info":[{"award-number":["81870363"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"science and technology departments of Sichuan province","award":["2020JDTD0025"],"award-info":[{"award-number":["2020JDTD0025"]}]},{"DOI":"10.13039\/501100008402","name":"Chengdu University of Traditional Chinese Medicine","doi-asserted-by":"publisher","award":["600242241005"],"award-info":[{"award-number":["600242241005"]}],"id":[{"id":"10.13039\/501100008402","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myopathy encompasses a group of diseases characterized by abnormalities in both muscle function and structure. However, the underlying regulatory mechanisms of newly formed myofiber development remain poorly defined. No promising therapeutic approach has been developed, but numerous medication options are available to alleviate symptoms. Our previous studies demonstrated that adenosine kinase (ADK) is critical in regulating adenosine metabolism, pathological angiogenesis, pathological vascular remodeling, and vascular inflammatory diseases. Adenosine dynamically distributes between extracellular and intracellular, and adenosine concentration regulates ADK expression. However, the mechanism by which adenosine triggers an ADK-dependent intracellular signaling pathway to regulate skeletal muscle regeneration is not well defined. This study aimed to evaluate whether the adenosine-induced intracellular signaling pathway is involved in regulating myopathy, and how it regulates the development of newly formed myofibers. In this study, an intramuscular injection of cardiotoxin was used to induce a skeletal muscle injury model; satellite cells and C2C12 cells were employed. Whether adenosine regulates satellite cell activity, new myofiber formation and differentiation, as well as fusion of myofibers, were determined by H&amp;E staining, BrdU incorporation assay, and spheroid sprouting assay. Interaction between ADK and PFKFB3 was evaluated by IF staining, PPI network analysis, molecular docking simulation, and CO-immunoprecipitation assay. The results demonstrated that adenosine dynamically distributes between extracellular and intracellular through concentrative nucleoside transports or equilibrative nucleoside transporters, and it rapidly induces an ADK-dependent intracellular signaling pathway, which interacts with PFKFB3-mediated glycolytic metabolism to promote satellite cell activity, new myofiber formation, differentiation, and fusion, and eventually enhances skeletal muscle regeneration after injury stress. The remarkable endogenous regeneration capacity of skeletal muscle, which is regulated by adenosine-triggered intracellular signaling, presents a promising therapeutic strategy for treating muscle trauma and muscular dystrophies.<\/jats:p>","DOI":"10.3390\/ijms262412184","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T16:42:05Z","timestamp":1766076125000},"page":"12184","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adenosine Triggers an ADK-Dependent Intracellular Signaling Pathway Interacts PFKFB3-Mediated Glycolytic Metabolism to Promote Newly Formed Myofibers Development"],"prefix":"10.3390","volume":"26","author":[{"given":"Xiao","family":"Wu","sequence":"first","affiliation":[{"name":"College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dawei","family":"Zeng","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baojia","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cong","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Nie","sequence":"additional","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine, School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liangqin","family":"Shi","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"R13","DOI":"10.1530\/JOE-13-0567","article-title":"Endocrine regulation of fetal skeletal muscle growth: Impact on future metabolic health","volume":"221","author":"Brown","year":"2014","journal-title":"J. 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