Abstract
Duchenne muscular dystrophy (DMD) is a human genetic disease characterized by fibrosis and severe muscle weakness. Currently, there is no effective treatment available to prevent progressive fibrosis in skeletal muscles. The serum- and glucocorticoid-inducible kinase SGK1 regulates a variety of physiological functions and participates in fibrosis stimulation. Here, we investigated whether SGK1 influences structure, function and/or fibrosis of the muscles from the mdx mouse, an animal model for DMD. As expected, mdx muscles showed the typical pathological features of muscular dystrophy including fiber size variations, central nuclei of muscle fibers, fibrosis in the diaphragm, and force reduction by 30–50 %. Muscles from sgk1 -/- mice were histologically overall intact and specific force was only slightly reduced compared to wild-type muscles. Surprisingly, soleus and diaphragm muscles of mdx/sgk1 -/- mice displayed forces close to wild-type levels. Most muscle fibers of the double mutants contained central nuclei, but fibrosis was not observed in any of the tested limb and diaphragm muscles. We conclude that the sole lack of SGK1 in mouse muscle does not lead to pronounced changes in muscle structure and function. However, dystrophin-deficient mdx muscle seems to benefit from SGK1 deficiency. SGK1 appears to be an important enzyme in the process of fibrotic remodeling and subsequent weakness of dystrophin-deficient mouse muscle.
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Acknowledgments
We are grateful to Ms. H. Kenk for the expert technical assistance and we thank U. Lendeckel for kindly providing the anti-SGK1 antibody. This work was supported by project grants from the European Commission (FP7-REGPOT-2010, grant no. 264143) and Deutsche Duchenne Stiftung der aktion benni & co. e.V. to H. B. and a Gerhardt Domagk scholarship of the University Medicine Greifswald to Martin Steinberger, F. L. obtained support from the Deutsche Forschungsgemeinschaft (DFG).
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Steinberger, M., Föller, M., Vogelgesang, S. et al. Lack of the serum- and glucocorticoid-inducible kinase SGK1 improves muscle force characteristics and attenuates fibrosis in dystrophic mdx mouse muscle. Pflugers Arch - Eur J Physiol 467, 1965–1974 (2015). https://doi.org/10.1007/s00424-014-1645-5
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DOI: https://doi.org/10.1007/s00424-014-1645-5