Aumento paralelo das integrinas 7 e β1 previne as alterações musculares em camundongos com distrofia muscular

USA - estudos prévios já tinham demonstrado que o aumento da integrina 7 diminuia as alterações patológicas em modelos de distrofia muscular em camundongo. Nesta pesquisa os autores que o aumento concomitante das integrinas 7 e β1 é fundamental para o máximo benefício na redução das alterações degenerativas da distrofia muscular.

O resumo em inglês pode ser lido abaixo:

(FASEB Meeting, 2010) Parallel increasing of 7 and β1 integrin prevents muscular dystrophy in mdx mice

Jianming Liu1,2 and Stephen J. Kaufman2

1 Cell & Tissue Biology, University of California San Francisco, San Francisco, CA
2 Cell & Developmental Biology, University of Illinois, Urbana, IL

Duchenne muscular dystrophy is a devastating muscle disease that is ultimately lethal. Without the dystrophin complex that normally connects myofibers actin cytoskeleton to the laminin in extracellular matrix, membrane integrity of muscle fibers is greatly compromised. One potential therapeutic treatment for muscular dystrophy is to augment the transmembrane linkages by increasing other laminin receptors such as integrins. We previously showed that transgenic expression of 7 chain of the integrin in skeletal muscle effectively alleviates the dystrophic pathologies and extends the lifespan of mdx/utrn–/– mice. However, expression of 7 chain alone in mdx mice provided little improvement of skeletal muscle health. We now found that in transgenic mice expressing high levels of 7 chain, relatively little 7 was targeted to the muscle membrane and thus mostly remained within myofibers, likely due to limiting amount of the endogenous integrin β1 protein. We then demonstrated that overexpress β1D integrin results in 7 chain increase in wild type mice and that commensurate increase of β1 chains in 7 transgenic mice promotes more functional heterodimers targeting to the sarcolemma. Likewise, increasing the amount of β1D integrin in 7-mdx transgenic mice also promotes localization of the 7β1 integrin to the sarcolemma and protects against muscle damages caused by the muscular dystrophy. Our results suggest that parallel increases of and β integrin subunits are essential to achieve maximal beneficial effects of integrin based therapies for muscular dystrophy.

Fonte: http://distrofiamuscular.net/noticias.htm