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• W2034603061 endingPage "e0120325" @default.
• W2034603061 startingPage "e0120325" @default.
• W2034603061 abstract "Duchenne muscular dystrophy (DMD), the most common and severe type of dystrophinopathy, is an X-linked recessive genetic disease caused by the absence of dystrophin, which leads to fragility and vulnerability of the sarcolemma to mechanical stretching with increased membrane permeability. Currently, glucocorticoids such as prednisolone are the only medication available for DMD. However, molecular pathways responsible for this effect are still unclear. In addition, it remains unclear whether sex-related factors, including pregnancy and the postpartum period, affect the phenotype of dystrophinopathy. Here, we report the amelioration of muscle membrane permeability in the diaphragm muscle of pregnant and postpartum, but not in nulliparous, mdx mice, an animal model for DMD, during the physiological surge of corticosterone, the most abundant glucocorticoid in rodents. Cultures of single muscle fibers and myotubes isolated from mdx mouse diaphragm demonstrate resistance to hypo-osmotic shock when treated with corticosterone but not with estradiol or progesterone. This corticosterone-mediated resistance was diminished by an antagonist of corticosterone, indicating that the glucocorticoid-glucocorticoid receptor axis plays a role in this membrane stabilization effect on muscle. Moreover, subcutaneous injection of corticosterone into mdx mice showed decreased membrane permeability. This is the first report to demonstrate that pregnancy-related resistance to muscle fiber damage in mdx mice due to the membrane stabilization effect of corticosterone. We also propose that this membrane stabilization effect is exerted through annexin A1 up-regulation as the molecular mechanisms of glucocorticoid effects on DMD muscle. Furthermore, single muscle fiber culture studies provide a sensitive chemical screening platform for muscular dystrophies." @default.
• W2034603061 created "2016-06-24" @default.
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• W2034603061 date "2015-03-16" @default.
• W2034603061 modified "2023-09-27" @default.
• W2034603061 title "Pregnancy-Induced Amelioration of Muscular Dystrophy Phenotype in mdx Mice via Muscle Membrane Stabilization Effect of Glucocorticoid" @default.
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• W2034603061 doi "https://doi.org/10.1371/journal.pone.0120325" @default.
• W2034603061 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4361742" @default.
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• W2034603061 hasPublicationYear "2015" @default.
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