{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T08:40:44Z","timestamp":1780562444290,"version":"3.54.1"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":65,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biochemistry Research International"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>L\u2010arginine induces the expression of utrophin in skeletal muscle cells, so it has been proposed as a pharmacological treatment to attenuate the symptoms of Duchenne muscular dystrophy (DMD). On the other hand, it has been described that one of the pathways that participates in the expression of utrophin in muscle is the Neuregulin\u20101 (NRG\u20101)\/ErbB receptors pathway. Several studies have postulated that disintegrin and metalloprotease\u201017 (ADAM17) causes the proteolytic processing of NRG of transmembrane, allowing the release of NRG to the medium, which when joining its ErbB receptor activates the signaling pathway that triggers utrophin transcription. The aim of this study was to evaluate the effect of L\u2010arginine in the activation of NRG\u20101\/ErbB pathway and utrophin mRNA levels in C2C12\u2009cells, and the participation of ADAM17 in this process. Our results indicate that L\u2010arginine induces phosphorylation of ErbB2 and increases utrophin mRNA levels in C2C12 myotubes, with a maximum increase of 2\u2010fold at 4\u2009h post\u2010stimulation. This effect is not observed when the myotubes are stimulated in the presence of GM6001 (general metalloprotease inhibitor) or PD\u2010158780 (specific inhibitor of ErbB receptor phosphorylation). Experiments performed by flow cytometry suggest that L\u2010arginine stimulates ADAM17 activation in our study model. Furthermore, immunofluorescence analysis supports our findings that L\u2010arginine stimulates ADAM17 increase in treated myotubes. However, our results using pharmacological inhibitors suggest that ADAM17 does not participate in utrophin expression in C2C12\u2009cells treated with L\u2010arginine. The results obtained help to clarify the mechanism of action of L\u2010arginine in the expression of utrophin in muscle cells, which will contribute to the design of new therapeutic strategies in pathologies such as DMD.<\/jats:p>","DOI":"10.1155\/bri\/2171745","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T23:49:34Z","timestamp":1741736974000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["L\u2010Arginine Activates the Neuregulin\u20101\/ErbB Receptor Signaling Pathway and Increases Utrophin mRNA Levels in 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