Activation of serum/glucocorticoid-induced kinase 1 (SGK1) is important to maintain skeletal muscle homeostasis and prevent atrophy.
Bottom Line: Here, we describe a mechanism underlying muscle preservation and translate it to non-hibernating mammals.Although Akt has an established role in skeletal muscle homeostasis, we find that serum- and glucocorticoid-inducible kinase 1 (SGK1) regulates muscle mass maintenance via downregulation of proteolysis and autophagy as well as increased protein synthesis during hibernation.Our results identify a novel therapeutic target to combat loss of skeletal muscle mass associated with muscle degeneration and atrophy.
Affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.Show MeSH
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Mentions: In order to assess whether SGK1 expression protects against targeted disuse atrophy, we transfected TA muscles via electroporation with plasmids encoding Sgk1 WT (Sgk1WT), Kinase Dead (Sgk1KD) and Constitutively Active Sgk1 (Sgk1CA) all fused to EGFP. One hindlimb was immobilized by stapling (Burks et al, 2011), and the plasmids were injected into both the immobilized and the contralateral non-immobilized muscles. After 9 days, both TA muscles were assessed for plasmid expression and morphometric measurements. Co-immunostaining for laminin γ-1 ensured that plasmid expression was confined to skeletal muscle fibers and not within extracellular space. Gene transfection efficiency was determined by calculating the cross sectional area of GFP positive muscle fibers expressed as a percentage of the total cross sectional area (Schertzer et al, 2006). All constructs revealed a transfection efficiency of 58.6–78.5% (Supporting Information Fig S6D). Transfection of contralateral, non-immobilized TA muscles did not show any significant changes in muscle fiber size or morphology with any of the plasmids injected (Supporting Information Fig S6B). However, in the immobilized limb transfection of Sgk1CA completely prevented muscle atrophy when compared to GFP only, Sgk1WT and Sgk1KD (Fig 7A–C and Supporting Information Fig S6A). Importantly, skeletal muscle atrophy was only prevented by transfection of the constitutively active form of Sgk1.
Affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.