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Am J Physiol Cell Physiol 294: C627-C640, 2008. First published November 28, 2007; doi:10.1152/ajpcell.00329.2007
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MUSCLE CELL BIOLOGY AND CELL MOTILITY

Increasing {alpha}7β1-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression

Jianming Liu,1 Dean J. Burkin,2 and Stephen J. Kaufman1

1Department of Cell and Developmental Biology, University of Illinois, Urbana, Illinois; and 2Department of Pharmacology, University of Nevada School of Medicine, Reno, Nevada

Submitted 27 July 2007 ; accepted in final form 22 November 2007

The dystrophin-glycoprotein complex maintains the integrity of skeletal muscle by associating laminin in the extracellular matrix with the actin cytoskeleton. Several human muscular dystrophies arise from defects in the components of this complex. The {alpha}7β1-integrin also binds laminin and links the extracellular matrix with the cytoskeleton. Enhancement of {alpha}7-integrin levels alleviates pathology in mdx/utrn–/– mice, a model of Duchenne muscular dystrophy, and thus the integrin may functionally compensate for the absence of dystrophin. To test whether increasing {alpha}7-integrin levels affects transcription and cellular functions, we generated {alpha}7-integrin-inducible C2C12 cells and transgenic mice that overexpress the integrin in skeletal muscle. C2C12 myoblasts with elevated levels of integrin exhibited increased adhesion to laminin, faster proliferation when serum was limited, resistance to staurosporine-induced apoptosis, and normal differentiation. Transgenic expression of eightfold more integrin in skeletal muscle did not result in notable toxic effects in vivo. Moreover, high levels of {alpha}7-integrin in both myoblasts and in skeletal muscle did not disrupt global gene expression profiles. Thus increasing integrin levels can compensate for defects in the extracellular matrix and cytoskeleton linkage caused by compromises in the dystrophin-glycoprotein complex without triggering apparent overt negative side effects. These results support the use of integrin enhancement as a therapy for muscular dystrophy.

myoblast proliferation; integrin transgenic mice; microarray


Address for reprint requests and other correspondence: S. J. Kaufman, Dept. of Cell and Developmental Biology, Univ. of Illinois, 601 S. Goodwin Ave., B107 Chemical and Life Sciences Laboratory, Urbana, IL 61801 (e-mail: stephenk{at}uiuc.edu)






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