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Genetic and pharmacological regulation of the endocannabinoid CB1 receptor in Duchenne muscular dystrophy

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Item Type:Article
Title:Genetic and pharmacological regulation of the endocannabinoid CB1 receptor in Duchenne muscular dystrophy
Creators Name:Iannotti, F.A. and Pagano, E. and Guardiola, O. and Adinolfi, S. and Saccone, V. and Consalvi, S. and Piscitelli, F. and Gazzerro, E. and Busetto, G. and Carrella, D. and Capasso, R. and Puri, P.L. and Minchiotti, G. and Di Marzo, V.
Abstract:The endocannabinoid system refers to a widespread signaling system and its alteration is implicated in a growing number of human diseases. However, the potential role of endocannabinoids in skeletal muscle disorders remains unknown. Here we report the role of the endocannabinoid CB1 receptors in Duchenne's muscular dystrophy. In murine and human models, CB1 transcripts show the highest degree of expression at disease onset, and then decline overtime. Similar changes are observed for PAX7, a key regulator of muscle stem cells. Bioinformatics and biochemical analysis reveal that PAX7 binds and upregulates the CB1 gene in dystrophic more than in healthy muscles. Rimonabant, an antagonist of CB1, promotes human satellite cell differentiation in vitro, increases the number of regenerated myofibers, and prevents locomotor impairment in dystrophic mice. In conclusion, our study uncovers a PAX7-CB1 cross talk potentially exacerbating DMD and highlights the role of CB1 receptors as target for potential therapies.
Keywords:Arachidonic Acids, Base Sequence, Biomarkers, CB1 Cannabinoid Receptor, Diglycerides, Duchenne Muscular Dystrophy, Endocannabinoids, Genetic Transcription, Glycerides, HEK293 Cells, Inbred C57BL Mice, Inbred mdx Mice, Luciferases, Messenger RNA, Motor Activity, Muscle Cells, PAX7 Transcription Factor, Regeneration, Rimonabant, Skeletal Muscle, Animals, Mice
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group (U.K.)
Volume:9
Number:1
Page Range:3950
Date:27 September 2018
Official Publication:https://doi.org/10.1038/s41467-018-06267-1
PubMed:View item in PubMed

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