Effect of cyclic stretch on β1D-integrin expression and activation of FAK and RhoA
- 1 June 2007
- journal article
- Published by American Physiological Society in American Journal of Physiology-Cell Physiology
- Vol. 292 (6), C2057-C2069
- https://doi.org/10.1152/ajpcell.00493.2006
Abstract
Integrins play a pivotal role in proliferation, differentiation, and survival in skeletal and cardiac myocytes. The β1D-isoform of the β1-integrin is specifically expressed in striated skeletal muscle. However, little is known about the role and the mechanisms by which the splice variant β1D-integrin regulates myogenesis and mechanotransduction. We observed that cyclic mechanical stretch increases β1D-integrin protein levels and activates the downstream cytoskeletal signaling proteins focal adhesion kinase (FAK) and RhoA. Elimination of native β1D-integrin expression by RNA interference in immature developing myoblasts abolished stretch-induced increases in FAK phosphorylation and further downregulated RhoA activity. Blocking of β1D-integrin expression prevented myocellular fusion to form multinucleated mature myotubes. Restoration of human β1D-integrin expression in β1D-integrin-deficient cells partially restored myotube formation. The onset of myofusion also requires the generation of nitric oxide (NO). The release of NO affects cytoskeletal proteins by mediating RhoA activity and protein degradation. Our previous study demonstrated that stretch-induced NO positively modulates mechanical properties of differentiating skeletal myocytes. We found a significant decrease in NO production and apparent elastic modulus in β1D-integrin-deficient cells, suggesting signaling interactions between β1D-integrin and neuronal NO synthase to mediate mechanotransduction and myogenesis in skeletal myocytes. These results suggest that, in addition to regulating differentiation, the β1D-integrin isoform plays a critical role in the response of skeletal myoblasts to cyclic stretch by activating the downstream components of FAK and RhoA activity and affecting NO release.Keywords
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