Abstract
The excessive accumulation of collagens (fibrosis) impairs the function of vital tissues and organs. Fibrosis is a hallmark of severe muscular dystrophies, such as the incurable Duchenne Muscular Dystrophy (DMD), where skeletal muscle is substituted by scar (fibrotic) tissue as disease advances. One of the major obstacles in increasing our ability to combat fibrosis-driven muscular dystrophy progression is that no optimal in vivo models of muscle fibrosis are currently available, limiting fibrosis research and the development of novel therapies. In this chapter we describe different experimental strategies to accelerate and enhance muscle fibrosis in vivo in the widely used animal model for DMD, the mdx mouse. Since excessive tissue scarring also hampers the normal regeneration process after muscle injury, we have extended these fibrogenic strategies to the muscle of normal (non-diseased) mice. These strategies will allow fibrosis induction and assessment in a wide array of genetically modified mouse lines in physiological and pathological conditions of muscle regeneration. They should eventually improve our ability to combat fibrosis and foster muscle regeneration in DMD.
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Acknowledgment
Work in the authors’ laboratory has been supported by MINECO-Spain (SAF2012-38547, PIE1400061), AFM, E-Rare, Fundació Marató TV3, MDA, EU-FP7 (Myoage, Optistem, and Endostem), and DuchennePP-NL. PP was supported by a postdoctoral fellowship from AFM. The help of Drs. Antonio L Serrano, E. Perdiguero, Y. Kharraz, and M. Jardí in the original studies where these protocols were first used is greatly appreciated.
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Pessina, P., Muñoz-Cánoves, P. (2016). Fibrosis-Inducing Strategies in Regenerating Dystrophic and Normal Skeletal Muscle. In: Kyba, M. (eds) Skeletal Muscle Regeneration in the Mouse. Methods in Molecular Biology, vol 1460. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3810-0_7
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DOI: https://doi.org/10.1007/978-1-4939-3810-0_7
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