Integrin β1D regulates skeletal myogenesis and mechanotransduction.

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Integrins play a pivotal role in proliferation, differentiation and survival in skeletal myocytes. The isoform β1D is specifically expressed in striated skeletal muscle and is developmentally regulated. We investigated whether integrin β1D mediates myogenesis and mechanotransduction in skeletal myocytes. We found that mechanical stretch accelerated differentiation of skeletal myoblasts, which correlated with considerable increases in integrin β1D as well as the downstream signaling events, FAK phosphorylation and RhoA activity. Inhibition of integrin β1D expression in myoblasts with DNA vector generated short hairpin siRNA (shRNA) prevented fusion and myofiber formation and impaired stress fiber formation. Similarly, inhibition of RhoA activity with C3 transferase, a specific inhibitor of Rho small GTPases, attenuated differentiation and the formation of actin-cytoskeleton were observed as well. Moreover, suppression of integrin β1D completely abolished the stretch-induced increases of FAK Tyr397 phosphorylation and RhoA activity levels. Nitric oxide is involved in myodifferentiation and is increased after stretch. A significant decrease in NO production and apparent elastic modulus, Eapp were found in integrin β1D deficient cells under static and stretch conditions. Taken together, these data suggest integrin β1D mediates differentiation by regulating RhoA activity and signaling interactions between integrin β1D and nNOS may influence myogenesis and mechanotransduction in skeletal myocytes.