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REPORT

MUSCLE CELL BIOLOGY AND CELL MOTILITY

₇₁-Integrin regulates mechanotransduction and prevents skeletal muscle injury

Department of Cell and Developmental Biology, University of Illinois, Urbana, Illinois

Submitted 1 July 2005 ; accepted in final form 11 January 2006

ABSTRACT

₇₁-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 ₇₁-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 ₇BX2 chain. We report here that increasing ₇₁-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 ₇₁ protein. These experiments provide the first evidence that ₇₁-integrin is a negative regulator of mechanotransduction in vivo and provides resistance to exercise-induced muscle damage.

downhill running exercise; MAP kinase; AKT; mTOR; p70^S6k

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