Nambu Yoshinori, Matsumura Tsuyoshi, Machida Kyoka, Tsutsumi Rie, Hata Shoji, Shinkai-Ouchi Fumiko, Ono Yasuko, Osawa Kayo, Shirakawa Taku, Bo Ryosuke, Nishio Hisahide, Sakaue Hiroshi, Awano Hiroyuki, Matsuo Masafumi
Department of Pediatrics, Graduate School of Medicine, Kobe University, Kobe, Japan.
Department of Neurology, NHO Osaka Toneyama Medical Center, Osaka, Japan.
Muscle Nerve. 2025 Mar;71(3):442-445. doi: 10.1002/mus.28340. Epub 2025 Jan 8.
A 20 kDa fragment at the N-terminus 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-terminal fragment is presumed to be a product of degradation by a protein-degrading 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.
We measured urine titin by ELISA in two genetically confirmed limb-girdle muscular dystrophy type R1(LGMDR1) patients, 11 other LGMD patients, and five healthy controls. Five Capn3-/- and nine wild-type mice were also examined.
Urine titin in LGMDR1 patients was ~100-fold higher than in controls (median 112.3 vs. 1.3 pmol/mg Cr, p < 0.0001), with no difference between LGMDR1 and other LGMD subtypes. Similarly, urine titin levels in Capn3-/- mice were more than four times higher than normal (p < 0.01).
These results suggest the involvement of other protein-degrading enzymes leading to the production of the N-terminal fragment.
肌联蛋白N端的一个20 kDa片段在杜氏肌营养不良症（DMD）患者尿液中大量排出，使尿肌联蛋白成为肌肉分解的一个重要生物标志物。这个N端片段被认为是蛋白降解酶钙蛋白酶3降解的产物；然而，钙蛋白酶3是否是必需的仍不清楚。我们旨在确定在没有钙蛋白酶3的情况下尿肌联蛋白是否会升高。
我们通过酶联免疫吸附测定法（ELISA）测量了两名经基因确诊的R1型肢带型肌营养不良症（LGMDR1）患者、其他11名肢带型肌营养不良症患者和5名健康对照者的尿肌联蛋白。还检测了5只Capn3基因敲除小鼠和9只野生型小鼠。
LGMDR1患者的尿肌联蛋白比对照组高约100倍（中位数分别为112.3和1.3 pmol/mg肌酐，p < 0.0001），LGMDR1与其他肢带型肌营养不良症亚型之间无差异。同样，Capn3基因敲除小鼠的尿肌联蛋白水平比正常水平高出四倍多（p < 0.01）。
这些结果表明其他蛋白降解酶参与了N端片段的产生。
