Journal
LIFE SCIENCES
Volume 281, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2021.119756
Keywords
Duchenne muscular dystrophy; mdx; ADAMTS1; Fibrosis; Muscle strength
Funding
- Shaanxi Provincial Scientific and Techno-logical Project [2015SF214]
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In this study, it was found that ADAMTS1 levels were increased in mdx mice lacking dystrophin and DMD patients. Treatment with anti-ADAMTS1 improved muscle function, reduced muscle fibrosis, and enhanced muscle strength in mdx mice. This suggests that ADAMTS1 may be a potential target for developing new biological therapies for DMD.
Duchenne Muscular Dystrophy (DMD) is caused by mutations in the dystrophin gene, accompanied by aberrant extracellular matrix synthesis and muscle damage. ADAMTS1 metalloproteinase was reported increased in dystrophin-deficient mdx mouse. The aim of this study was to explore the role of ADAMTS1 in muscle function, fibrosis and damage, and respiratory function of mdx mice. 102 DMD patients and their mothers were included in this study. Multiplex ligation dependent probe amplification (MLPA) assay and Next-generation sequencing (NGS) were adopted to do genetic diagnosis. Dystrophin-deficient mdx mice were treated with anti-ADAMTS1 antibody (anti-ADAMTS1) for three weeks. The results showed that ADAMTS1 was increased in gastrocnemius muscle of mdx mice and serum of DMD patients. Anti-ADAMTS1 treatment increased Versican transcription but suppressed versican protein expression. Besides, we found anti-ADAMTS1 improved muscle strength, diaphragm and extensor digitorum longus muscles functions in mdx mice. Meanwhile, muscle fibrosis and damage were attenuated in anti-ADAMTS1 treated dystrophic mice. In summary, anti-ADAMTS1 antibody relieved muscle dysfunction and fibrosis in dystrophic mice. It is suggested that ADAMTS1 is a potential target for developing new biological therapies for DMD.
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