Article

α7β1-Integrin regulates mechanotransduction and prevents skeletal muscle injury

Dept. of Cell and Developmental Biology, University of Illinois, Urbana, IL 61801, USA.
AJP Cell Physiology (Impact Factor: 3.67). 07/2006; 290(6):C1660-5. DOI: 10.1152/ajpcell.00317.2005
Source: PubMed

ABSTRACT Alpha7beta1-integrin links laminin in the extracellular matrix with the cell cytoskeleton and therein mediates transduction of mechanical forces into chemical signals. Muscle contraction and stretching ex vivo result in activation of intracellular signaling molecules that are integral to postexercise injury responses. Because alpha7beta1-integrin stabilizes muscle and provides communication between the matrix and cytoskeleton, the role of this integrin in exercise-induced cell signaling and skeletal muscle damage was assessed in wild-type and transgenic mice overexpressing the alpha7BX2 chain. We report here that increasing alpha7beta1-integrin inhibits phosphorylation of molecules associated with muscle damage, including the mitogen-activated protein kinases (JNK, p38, and ERK), following downhill running. Likewise, activation of molecules associated with hypertrophy (AKT, mTOR, and p70(S6k)) was diminished in mice overexpressing integrin. While exercise resulted in Evans blue dye-positive fibers, an index of muscle damage, increased integrin protected mice from injury. Moreover, exercise leads to an increase in alpha7beta1 protein. These experiments provide the first evidence that alpha7beta1-integrin is a negative regulator of mechanotransduction in vivo and provides resistance to exercise-induced muscle damage.

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    • "The basal side of the SCs expresses integrin a7b1, which links the cytoskeleton with laminin in the BM (Song et al., 1992; Burkin and Kaufman, 1999). It plays a major role in the transduction of strain-induced mechanical forces into chemical signals, which are involved in the regulation of myogenesis (Boppart et al., 2006). The apical side expresses M-cadherin that attaches the SC to the adjacent myofiber (Cornelison and Wold, 1997; Kuang et al., 2008). "
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    • "Recently, it was observed that a functional IGF-1 receptor is not necessary for overload-induced muscle hypertrophy in rats (Spangenburg et al., 2008); a finding which strengthens the case for the importance of direct mechanotransduction . It is beyond the scope of this paper to discuss the possible mechanisms by which tension is transduced into intracellular signals; the interested reader is referred to the reviews above and to recent original papers (Boppart et al., 2006; Hornberger et al., 2006; Spangenburg & McBride, 2006). Interestingly , there appears to be some overlap between the pathways activated by mechanical stimuli and those activated by growth factors (Tidball, 2005). "
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    • "The precise sequence of events that initiates sarcolemmal damage and the influx of Ca ions that can result in myofibre necrosis especially in dystrophic muscles, are still unclear (Whitehead et al., 2006). The involvement of 71 integrin that binds laminin (Boppart et al., 2006), ADAM12 (Moghadaszadeh et al., 2003), inflammatory cells and inflammatory cytokines (especially TNF) (Hodgetts et al., 2006; Radley and Grounds, 2006) emphasize the importance of extracellular factors in myofibre susceptibility to necrosis. "
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