{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:06:36Z","timestamp":1790841996552,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,9,14]],"date-time":"2018-09-14T00:00:00Z","timestamp":1536883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007393","name":"Association Fran\u00e7aise contre les Myopathies","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007393","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["PI15\/01537"],"award-info":[{"award-number":["PI15\/01537"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>This study was performed to test the therapeutic potential of obestatin, an autocrine anabolic factor regulating skeletal muscle repair, to ameliorate the Duchenne muscular dystrophy (DMD) phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Using a multidisciplinary approach, we characterized the ageing\u2010related preproghrelin\/GPR39 expression patterns in <jats:italic>tibialis anterior<\/jats:italic> (TA) muscles of 4\u2010, 8\u2010, and 18\u2010week\u2010old <jats:italic>mdx<\/jats:italic> mice (<jats:italic>n<\/jats:italic>\u00a0=\u00a03\/group) and established the effects of obestatin administration at this level in 8\u2010week\u2010old <jats:italic>mdx<\/jats:italic> mice (<jats:italic>n<\/jats:italic>\u00a0=\u00a05\/group). The findings were extended to <jats:italic>in vitro<\/jats:italic> effects on human immortalized DMD myotubes. An analysis of TAs revealed an age\u2010related loss of preproghrelin expression, as precursor of obestatin, in <jats:italic>mdx<\/jats:italic> mice. Administration of obestatin resulted in a significant increase in tetanic specific force (33.0%\u00a0\u00b1\u00a01.5%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), compared with control <jats:italic>mdx<\/jats:italic> mice. Obestatin\u2010treated TAs were characterized by reduction of fibres with centrally located nuclei (10.0%\u00a0\u00b1\u00a01.2%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) together with an increase in the number of type I fibres (25.2%\u00a0\u00b1\u00a01.7%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) associated to histone deacetylases\/myocyte enhancer factor\u20102 and peroxisome proliferator\u2010activated receptor\u2010gamma coactivator 1\u03b1 axis, and down\u2010regulation of ubiquitin E3\u2010ligases by inactivation of FoxO1\/4, indexes of muscle atrophy. Obestatin reduced the level of contractile damage and tissue fibrosis. These observations correlated with decline in serum creatine kinase (58.8\u00a0\u00b1\u00a015.2, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Obestatin led to stabilization of the sarcolemma by up\u2010regulation of utrophin, \u03b1\u2010syntrophin, \u03b2\u2010dystroglycan, and \u03b17\u03b21\u2010integrin proteins. These pathways were also operative in human DMD myotubes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results highlight the potential of obestatin as a peptide therapeutic for preserving muscle integrity in DMD, thus allowing a better efficiency of gene or cell therapy in a combined therapeutic approach.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12338","type":"journal-article","created":{"date-parts":[[2018,9,16]],"date-time":"2018-09-16T05:00:23Z","timestamp":1537074023000},"page":"1063-1078","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Improvement of Duchenne muscular dystrophy phenotype following obestatin treatment"],"prefix":"10.1002","volume":"9","author":[{"given":"Jessica","family":"Gonz\u00e1lez\u2010S\u00e1nchez","sequence":"first","affiliation":[{"name":"Laboratorio de Endocrinolog\u00eda Celular Instituto de Investigaci\u00f3n Sanitaria de Santiago (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS)  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agust\u00edn","family":"S\u00e1nchez\u2010Temprano","sequence":"additional","affiliation":[{"name":"Laboratorio de Endocrinolog\u00eda Celular Instituto de Investigaci\u00f3n Sanitaria de Santiago (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS)  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Cid\u2010D\u00edaz","sequence":"additional","affiliation":[{"name":"Laboratorio de Endocrinolog\u00eda Celular Instituto de Investigaci\u00f3n Sanitaria de Santiago (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS)  Santiago de Compostela 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