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Publication
Glucocorticoids enhance muscle endurance and ameliorate Duchenne muscular
dystrophy through a defined metabolic program.
Authors Morrison-Nozik A, Anand P, Zhu H, Duan Q, Sabeh M, Prosdocimo DA, Lemieux ME,
Nordsborg N, Russell AP, MacRae CA, Gerber AN, Jain MK, Haldar SM
Submitted By Submitted Externally on 8/8/2017
Status Published
Journal Proceedings of the National Academy of Sciences of the United States of America
Year 2015
Date Published
Volume : Pages 112 : E6780 - 9
PubMed Reference 26598680
Abstract Classic physiology studies dating to the 1930s demonstrate that moderate or
transient glucocorticoid (GC) exposure improves muscle performance. The
ergogenic properties of GCs are further evidenced by their surreptitious use as
doping agents by endurance athletes and poorly understood efficacy in Duchenne
muscular dystrophy (DMD), a genetic muscle-wasting disease. A defined molecular
basis underlying these performance-enhancing properties of GCs in skeletal
muscle remains obscure. Here, we demonstrate that ergogenic effects of GCs are
mediated by direct induction of the metabolic transcription factor KLF15,
defining a downstream pathway distinct from that resulting in GC-related muscle
atrophy. Furthermore, we establish that KLF15 deficiency exacerbates dystrophic
severity and muscle GC-KLF15 signaling mediates salutary therapeutic effects in
the mdx mouse model of DMD. Thus, although glucocorticoid receptor (GR)-mediated
transactivation is often associated with muscle atrophy and other adverse
effects of pharmacologic GC administration, our data define a distinct
GR-induced gene regulatory pathway that contributes to therapeutic effects of
GCs in DMD through proergogenic metabolic programming.




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