β1D chain increases α7β1 integrin and laminin and protects against sarcolemmal damage in mdx mice

Jianming Liu, Derek J. Milner, Marni D. Boppart, Robert S. Ross, Stephen J. Kaufman

Research output: Contribution to journalArticlepeer-review

Abstract

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 α7β1 integrin, the major laminin-binding integrin in skeletal muscle. Whereas transgenic over-expression of α7 chain may alleviate development of muscular dystrophy and extend the lifespan of severely dystrophic mdx/utrn-/- mice, further enhancing levels of α7 chain provided little additional membrane integrin and negligible additional improvement in mdx mice. We demonstrate here that normal levels of β1 chain limit formation of integrin heterodimer and that increasing β1D 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 β1D chain in vitro enhances transcription of α7 integrin and α2 laminin genes and the amounts of these proteins. Thus manipulation of β1D integrin expression offers a novel approach to enhance integrin-mediated therapy for muscular dystrophy.

Original languageEnglish (US)
Article numberddr596
Pages (from-to)1592-1603
Number of pages12
JournalHuman molecular genetics
Volume21
Issue number7
DOIs
StatePublished - Apr 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'β1D chain increases α7β1 integrin and laminin and protects against sarcolemmal damage in mdx mice'. Together they form a unique fingerprint.

Cite this