Skeletal myogenesis is coordinated by multiple signaling pathways that control cell adhesion/migration, survival and differentiation accompanied by muscle-specific gene expression. A cell surface protein Cdo is involved in cell contact-mediated promyogenic signals through activation of p38MAPK and AKT. Protein kinase C-related kinase 2 (PKN2/PRK2) is implicated in regulation of various biological processes, including cell migration, adhesion and death. It has been shown to interact with and inhibit AKT thereby inducing cell death. This led us to investigate the role of PKN2 in skeletal myogenesis and the crosstalk between PKN2 and Cdo. Like Cdo, PKN2 was upregulated in C2C12 myoblasts during differentiation and decreased in cells with Cdo depletion caused by shRNA or cultured on integrin-independent substratum. This decline of PKN2 levels resulted in diminished AKT activation during myoblast differentiation. Consistently, PKN2 overexpression-enhanced C2C12 myoblast differentiation, whereas PKN2-depletion impaired it, without affecting cell survival. PKN2 formed complexes with Cdo, APPL1 and AKT via its C-terminal region and this interaction appeared to be important for induction of AKT activity as well as myoblast differentiation. Furthermore, PKN2-enhanced MyoD-responsive reporter activities by mediating the recruitment of BAF60c and MyoD to the myogenin promoter. Taken together, PKN2 has a critical role in cell adhesion-mediated AKT activation during myoblast differentiation.
Prevention of age-associated reduction in muscle mass and function is required to manage a healthy life. Supplemental (-)-Epicatechin (EC) appears to act as a potential regulator for muscle growth and strength. However, its cellular and molecular mechanisms as a potential muscle growth agent have not been studied well. In the current study, we investigated a role of EC in differentiation of muscle progenitors to gain the molecular insight into how EC regulates muscle growth. EC enhanced myogenic differentiation in a dose-dependent manner through stimulation of promyogenic signaling pathways, p38MAPK and Akt. EC treatment elevated MyoD activity by enhancing its heterodimerization with E protein. Consistently, EC also positively regulated myogenic conversion and differentiation of fibroblasts. In conclusion, EC has a potential as a therapeutic or nutraceutical remedy to treat degenerative muscle diseases or age-related muscle weakness.
BackgroundGinsenoside Rg1 belongs to protopanaxatriol-type ginsenosides and has diverse pharmacological activities. In this report, we investigated whether Rg1 could upregulate muscular stem cell differentiation and muscle growth.MethodsC2C12 myoblasts, MyoD-transfected 10T1/2 embryonic fibroblasts, and HEK293T cells were treated with Rg1 and differentiated for 2 d, subjected to immunoblotting, immunocytochemistry, or immunoprecipitation.ResultsRg1 activated promyogenic kinases, p38MAPK (mitogen-activated protein kinase) and Akt signaling, that in turn promote the heterodimerization with MyoD and E proteins, resulting in enhancing myogenic differentiation. Through the activation of Akt/mammalian target of rapamycin pathway, Rg1 induced myotube growth and prevented dexamethasone-induced myotube atrophy. Furthermore, Rg1 increased MyoD-dependent myogenic conversion of fibroblast.ConclusionRg1 upregulates promyogenic kinases, especially Akt, resulting in improvement of myoblast differentiation and myotube growth.
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