First Author | Liu J | Year | 2012 |
Journal | Hum Mol Genet | Volume | 21 |
Issue | 7 | Pages | 1592-603 |
PubMed ID | 22180459 | Mgi Jnum | J:181562 |
Mgi Id | MGI:5311976 | Doi | 10.1093/hmg/ddr596 |
Citation | Liu J, et al. (2012) beta1D chain increases alpha7beta1 integrin and laminin and protects against sarcolemmal damage in mdx mice. Hum Mol Genet 21(7):1592-603 |
abstractText | The dystrophin-glycoprotein complex connects myofibers with extracellular matrix laminin. In Duchenne muscular dystrophy, this linkage system is absent and the integrity of muscle fibers is compromised. One potential therapy for addressing muscular dystrophy is to augment the amount of alpha7beta1 integrin, the major laminin-binding integrin in skeletal muscle. Whereas transgenic over-expression of alpha7 chain may alleviate development of muscular dystrophy and extend the lifespan of severely dystrophic mdx/utrn(-/-) mice, further enhancing levels of alpha7 chain provided little additional membrane integrin and negligible additional improvement in mdx mice. We demonstrate here that normal levels of beta1 chain limit formation of integrin heterodimer and that increasing beta1D chain in mdx mice results in more functional integrin at the sarcolemma, more matrix laminin and decreased damage of muscle fibers. Moreover, increasing the amount of beta1D chain in vitro enhances transcription of alpha7 integrin and alpha2 laminin genes and the amounts of these proteins. Thus manipulation of beta1D integrin expression offers a novel approach to enhance integrin-mediated therapy for muscular dystrophy. |