{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T18:54:48Z","timestamp":1787684088298,"version":"build-2784847793"},"reference-count":10,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:00:00Z","timestamp":1736294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009438","name":"National Center of Neurology and Psychiatry","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009438","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>A 20\u2009kDa fragment at the N\u2010terminus of titin is highly excreted in the urine of patients with Duchenne muscular dystrophy (DMD), making urine titin a prominent biomarker for muscle breakdown. This N\u2010terminal fragment is presumed to be a product of degradation by a protein\u2010degrading enzyme, calpain 3; however, whether calpain 3 is required remains unclear. We aimed to determine whether urine titin elevation occurs in the absence of calpain 3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We measured urine titin by ELISA in two genetically confirmed limb\u2010girdle muscular dystrophy type R1(LGMDR1) patients, 11 other LGMD patients, and five healthy controls. Five <jats:italic>Capn3<\/jats:italic>\u2212\/\u2212 and nine wild\u2010type mice were also examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Urine titin in LGMDR1 patients was ~100\u2010fold higher than in controls (median 112.3 vs. 1.3\u2009pmol\/mg Cr, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), with no difference between LGMDR1 and other LGMD subtypes. Similarly, urine titin levels in <jats:italic>Capn3<\/jats:italic>\u2212\/\u2212 mice were more than four times higher than normal (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These results suggest the involvement of other protein\u2010degrading enzymes leading to the production of the N\u2010terminal fragment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.28340","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T08:08:43Z","timestamp":1736323723000},"page":"442-445","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The N\u2010Terminal Fragment of Urine Titin Is Not a Product of Degradation by Calpain 3"],"prefix":"10.1002","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7979-1040","authenticated-orcid":false,"given":"Yoshinori","family":"Nambu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine Kobe University  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Matsumura","sequence":"additional","affiliation":[{"name":"Department of Neurology NHO Osaka Toneyama Medical Center  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoka","family":"Machida","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Metabolism, Institute of Biomedical Sciences Tokushima University  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rie","family":"Tsutsumi","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Metabolism, Institute of Biomedical Sciences Tokushima University  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoji","family":"Hata","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences Tokyo Metropolitan Institute of Medical Science  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiko","family":"Shinkai\u2010Ouchi","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences Tokyo Metropolitan Institute of Medical Science  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuko","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences Tokyo Metropolitan Institute of Medical Science  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayo","family":"Osawa","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences Kobe Tokiwa University  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Shirakawa","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences Kobe Tokiwa University  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Bo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine Kobe University  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisahide","family":"Nishio","sequence":"additional","affiliation":[{"name":"Department of Occupational Therapy, Faculty of Rehabilitation Kobe Gakuin University  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Sakaue","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Metabolism, Institute of Biomedical Sciences Tokushima University  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9846-4142","authenticated-orcid":false,"given":"Hiroyuki","family":"Awano","sequence":"additional","affiliation":[{"name":"Organization for Research Initiative and Promotion Tottori University  Yonago Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences Kobe Tokiwa University  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2016.00021"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(89)90185-8"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2014.03.012"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2017.11.024"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep39375"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aat6072"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ame2.12204"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2014.07.016"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-10-140"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/14017431.2020.1831052"}],"container-title":["Muscle &amp; Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.28340","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T14:25:58Z","timestamp":1745245558000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.28340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,8]]},"references-count":10,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1002\/mus.28340"],"URL":"https:\/\/doi.org\/10.1002\/mus.28340","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,8]]},"assertion":[{"value":"2024-02-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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