Alpha 7 integrin preserves the function of the extensor digitorum longus muscle in dystrophin-null mice

作者：Hakim Chady H; Burkin Dean J; Duan Dongsheng^*

来源：Journal of Applied Physiology, 2013, 115(9): 1388-1392.

DOI：10.1152/japplphysiol.00602.2013

• alpha(7)beta(1)-integrin
• dystrophin
• contractile force
• passive force
• EDL muscle
• DMD
• mdx4cv
• muscular dystrophy

The dystrophin-associated glycoprotein complex (DGC) and the alpha(7)beta(1)-integrin complex are two independent protein complexes that link the extracellular matrix with the cytoskeleton in muscle cells. These associations stabilize the sarcolemma during force transmission. Loss of either one of these complexes leads to muscular dystrophy. Dystrophin is a major component of the DGC. Its absence results in Duchenne muscular dystrophy (DMD). Because alpha(7)-integrin overexpression has been shown to ameliorate muscle histopathology in mouse models of DMD, we hypothesize that the alpha(7)beta(1)-integrin complex can help preserve muscle function. To test this hypothesis, we evaluated muscle force, elasticity, and the viscous property of the extensor digitorum longus muscle in 19-day-old normal BL6, dystrophin-null mdx4cv, alpha(7)-integrin-null, and dystrophin/alpha(7)-integrin double knockout mice. While nominal changes were found in single knockout mice, contractility and passive properties were significantly compromised in alpha(7)-integrin double knockout mice. Our results suggest that DGC and alpha(7)beta(1)-integrin complexes may compensate each other to maintain normal skeletal muscle function. alpha(7)beta(1)-Integrin upregulation may hold promise to treat not only histological, but also physiological, defects in DMD.

• 出版日期2013-11