Measurement of a MMP-2 degraded Titin fragment in serum reflects changes in muscle turnover induced by atrophy

作者：Sun S^*; Henriksen K; Karsdal M A; Armbrecht G; Belavy D L; Felsenberg D; Rittweger J; Wang Y; Zheng Q; Nedergaard A F

来源：Experimental Gerontology, 2014, 58: 83-89.

DOI：10.1016/j.exger.2014.07.016

• Titin
• MMP-2
• Muscle atrophy
• Dexamethasone
• Bed rest

Purpose: In this study we sought to determine whether a Titin peptide fragment can serve as a clinical biomarker for changes in muscle mass. %26lt;br%26gt;Methods: Mass spectrometry was used to identify Titin fragment in urine. An antibody against this Titin sequence was raised and used to develop a competitive ELISA assay for measurement in serum. Rat tissue extractions in the presence or absence of a series of proteases of interest were used to identify its enzymatic origin. A rat model of dexamethasone (DEX) induced muscle atrophy and a human 56-day bed rest study with and without vibration therapy were used to assess biological and clinical relevance. %26lt;br%26gt;Results: A technically robust ELISA measuring the Titin fragment was developed against a Titin peptide fragment identified in human urine. The fragment was shown to be produced primarily by MMP-2 cleavage of Titin. In the rat muscle DEX induced atrophy model, Titin-MMP2 fragment was decreased in the beginning of DEX treatment, and then significantly increased later on during DEX administration. In the human bed rest study, the Titin-MMP2 fragment was initially decreased 11.9 (+/- 3.7) % after 1 day of bed rest, and then gradually increased ending up at a 16.4 (+/- 4.6) % increase at day 47. %26lt;br%26gt;Conclusions: We developed a robust ELISA measuring a muscle derived MMP-2 generated Titin degradation fragment in rat and human serum. Importantly, the fragment can be measured in serum and that these levels are related to induction of skeletal muscle atrophy.

• 出版日期2014-10