1. Pathways implicated in tadalafil amelioration of duchenne muscular dystrophy
- Author
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De Arcangelis, Valeria, Strimpakos, Georgios, Gabanella, Francesca, Corbi, Nicoletta, Luvisetto, Siro, Magrelli, Armando, Onori, Annalisa, Passananti, Claudio, Pisani, Cinzia, Rome, Sophie, Severini, Cinzia, Naro, Fabio, Mattei, Elisabetta, Di Certo, Maria Grazia, Monaco, Lucia, Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University of Rome (DIAG), IBCN, National Research Council (CNR), IBPM, Consiglio Nazionale della Ricerca, Department of Molecular Medicine, Karolinska Institutet [Stockholm], National Centre for Rare Diseases, Istituto Superiore di Sanità, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Brain Research Institute, Department of Physiology and Pharmacology, University of Bristol [Bristol]-Medical Research Center for Synaptic Plasticity, AFM [14353/15586 ], Sapienza University [C26A135NE2 ], FIRB [RBAP109BLT], FARMM Onlus, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), and European Brain Research Institute [Rome, Italy] (EBRI)
- Subjects
Male ,pseudohypertrophic childhood muscular dystrophy ,mice ,myopathie de duchenne ,[SDV]Life Sciences [q-bio] ,Duchenne Muscular Dystrophy ,métabolisme des lipides ,souris ,DMD ,muscular dystrophy ,PDE5 ,tadalafil ,Tadalafil ,transcription factors ,Animals ,Muscle, Skeletal ,glyceride metabolism ,muscle squelettique ,Phosphodiesterase 5 Inhibitors ,Lipid Metabolism ,Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ,Up-Regulation ,Mice, Inbred C57BL ,Muscular Dystrophy, Duchenne ,régulation positive des récepteurs ,voluntary muscle ,Mice, Inbred mdx ,Female ,mdx ,phosphodiesterase ,facteur de transcription - Abstract
Numerous therapeutic approaches for Duchenne and Becker Muscular Dystrophy (DMD and BMD), the most common X-linked muscle degenerative disease, have been proposed. So far, the only one showing a clear beneficial effect is the use of corticosteroids. Recent evidence indicates an improvement of dystrophic cardiac and skeletal muscles in the presence of sustained cGMP levels secondary to a blocking of their degradation by phosphodiesterase five (PDE5). Due to these data, we performed a study to investigate the effect of the specific PDE5 inhibitor, tadalafil, on dystrophic skeletal muscle function. Chronic pharmacological treatment with tadalafil has been carried out in mdx mice. Behavioral and physiological tests, as well as histological and biochemical analyses, confirmed the efficacy of the therapy. We then performed a microarray-based genomic analysis to assess the pattern of gene expression in muscle samples obtained from the different cohorts of animals treated with tadalafil. This scrutiny allowed us to identify several classes of modulated genes. Our results show that PDE5 inhibition can ameliorate dystrophy by acting at different levels. Tadalafil can lead to (1) increased lipid metabolism; (2) a switch towards slow oxidative fibers driven by the up-regulation of PGC-1; (3) an increased protein synthesis efficiency; (4) a better actin network organization at Z-disk. J. Cell. Physiol. 230: 224-232, 2016. (c) 2015 Wiley Periodicals, Inc.
- Published
- 2016
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