Wnt/beta-catenin signaling activates growth-control genes during overload-induced skeletal muscle hypertrophy.
Beta-catenin is a transcriptional activator shown to regulate the embryonic, postnatal, and oncogenic growth of many tissues. In most research to date, beta-catenin activation has been the unique downstream function of the Wnt signaling pathway. However, in the heart, a Wnt-independent mechanism involving Akt- mediated phosphorylation of glycogen synthase kinase (GSK)-3beta was recently shown to activate beta-catenin and regulate cardiomyocyte growth. In this study, results have identified the activation of the Wnt/beta-catenin pathway during hypertrophy of mechanically overloaded skeletal muscle. Significant increases in beta-catenin were determined during skeletal muscle hypertrophy. In addition, the Wnt receptor, mFrizzled (mFzd)-1, the signaling mediator disheveled-1, and the transcriptional co-activator, lymphocyte enhancement factor (Lef)-1, are all increased during hypertrophy of the overloaded mouse plantaris muscle. Experiments also determined an increased association between GSK-3beta and the inhibitory frequently rearranged in advanced T cell-1 protein with no increase in GSK-3beta phosphorylation (Ser9). Finally, skeletal muscle overload resulted in increased nuclear beta-catenin/Lef-1 expression and induction of the transcriptional targets c-Myc, cyclin D1, and paired-like homeodomain transcription factor 2. Thus this study provides the first evidence that the Wnt signaling pathway induces beta-catenin/Lef-1 activation of growth-control genes during overload induced skeletal muscle hypertrophy.[1]References
- Wnt/beta-catenin signaling activates growth-control genes during overload-induced skeletal muscle hypertrophy. Armstrong, D.D., Esser, K.A. Am. J. Physiol., Cell Physiol. (2005) [Pubmed]
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