Inhibition of glycogen synthase kinase-3β attenuates glucocorticoid-induced suppression of myogenic differentiation in vitro

Zhenyu Ma, Zhigang Zhong, Zhenyang Zheng, Xing Ming Shi, Weixi Zhang

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Glucocorticoids are the only therapy that has been demonstrated to alter the progress of Duchenne muscular dystrophy (DMD), the most common muscular dystrophy in children. However, glucocorticoids disturb skeletal muscle metabolism and hamper myogenesis and muscle regeneration. The mechanisms involved in the glucocorticoid-mediated suppression of myogenic differentiation are not fully understood. Glycogen synthase kinase-3β (GSK-3β) is considered to play a central role as a negative regulator in myogenic differentiation. Here, we showed that glucocorticoid treatment during the first 48 h in differentiation medium decreased the level of phosphorylated Ser9-GSK-3β, an inactive form of GSK-3β, suggesting that glucocorticoids affect GSK-3β activity. We then investigated whether GSK-3β inhibition could regulate glucocorticoid-mediated suppression of myogenic differentiation in vitro. Two methods were employed to inhibit GSK-3β: pharmacological inhibition with LiCl and GSK-3β gene knockdown. We found that both methods resulted in enhanced myotube formation and increased levels of muscle regulatory factors and muscle-specific protein expression. Importantly, GSK-3β inhibition attenuated glucocorticoid- induced suppression of myogenic differentiation. Collectively, these data suggest the involvement of GSK-3β in the glucocorticoid-mediated impairment of myogenic differentiation. Therefore, the inhibition of GSK-3β may be a strategy for preventing glucocorticoid-induced muscle degeneration.

Original languageEnglish (US)
Article numbere105528
JournalPloS one
Volume9
Issue number8
DOIs
StatePublished - Aug 15 2014

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Glycogen Synthase Kinase 3
glucocorticoids
Glucocorticoids
Muscle
muscular dystrophy
muscle development
Muscles
muscles
In Vitro Techniques
tau-protein kinase
Gene Knockdown Techniques
Duchenne Muscular Dystrophy
Muscle Development
Muscle Proteins
Muscular Dystrophies
Skeletal Muscle Fibers
Metabolism
skeletal muscle
Regeneration
Skeletal Muscle

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Inhibition of glycogen synthase kinase-3β attenuates glucocorticoid-induced suppression of myogenic differentiation in vitro. / Ma, Zhenyu; Zhong, Zhigang; Zheng, Zhenyang; Shi, Xing Ming; Zhang, Weixi.

In: PloS one, Vol. 9, No. 8, e105528, 15.08.2014.

Research output: Contribution to journalArticle

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