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PTEN Inhibition Ameliorates Muscle Degeneration and Improves Muscle Function in a Mouse Model of Duchenne Muscular Dystrophy

PTEN Inhibition Ameliorates Muscle Degeneration and Improves Muscle Function in a Mouse Model of Duchenne Muscular Dystrophy

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.13.249961v1?rss=1 Authors: Yue, F., Song, C., Huang, D., Narayanan, N., Qiu, J., Jia, Z., Yuan, Z., Oprescu, S. N., Roseguini, B. T., Deng, M., Kuang, S. Abstract: Duchenne Muscular Dystrophy (DMD) is caused by mutation of the muscle membrane protein dystrophin and characterized by severe degeneration of myofibers, progressive muscle wasting and loss of mobility, ultimately cardiorespiratory failure and premature death. Here we report that skeletal muscle-specific knockout (KO) of Phosphatase and tensin homolog (Pten) gene in an animal model of DMD (mdx mice) alleviates myofiber degeneration and restores muscle function without increasing tumor incidences. Specifically, Pten KO normalizes myofiber size and prevents muscular atrophy, and improves grip strength and exercise performance of mdx mice. Pten KO also reduces fibrosis and inflammation; and ameliorates muscle pathology in mdx mice. Moreover, we found that Pten KO upregulates extracellular matrix and basement membrane components positively correlated to wound healing, but suppresses negative regulators of wound healing and lipid biosynthesis; and restores the integrity of muscle basement membrane in mdx mice. Importantly, pharmacological inhibition of PTEN similarly ameliorates muscle pathology and improves muscle integrity and function in mdx mice. Our finding provides evidence that PTEN inhibition may represent a potential therapeutic strategy to restore muscle function in DMD. Copy rights belong to original authors. Visit the link for more info

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