The Alpha7beta1 Integrin in Skeletal Muscle and Muscular Dystrophy

This thesis examines the effects of enhancing alpha7 integrin on cellular functions and global gene expression in myoblasts and skeletal muscle. I found that 3-fold more alpha7 integrin promotes myoblast adhesion, proliferation and resistance to apoptosis without affecting differentiation. In addition, 8-fold more alpha7 integrin in skeletal muscle is not toxic and has no adverse effects in alpha7 integrin transgenic mice. Moreover, enhancing alpha7 integrin only minimally affects global gene expression in myoblasts and skeletal muscle. Thus, increasing alpha7 integrin is a promising therapeutic approach for treating Duchenne muscular dystrophy as it can reinforce the association between the extracellular matrix and actin cytoskeleton without interfering with normal cell functions or gene expression. In this dissertation I also demonstrate that beta1 integrin is a limiting factor for the compensatory effects of enhanced alpha7 integrin in skeletal muscle and my results suggest that increasing both alpha7 and beta1 integrin chains may be a more effective strategy for treating muscular dystrophy. In addition, I report the discovery of a species-specific proteolytic cleavage of the alpha7 integrin chain and demonstrate this cleavage regulates integrin mediated cellular functions. The potential involvement of this proteolytic cleavage in muscular dystrophy is also discussed. Together, this dissertation explores the functions of the alpha7beta1 integrin in skeletal muscle and its potential use as a treatment for muscular dystrophy.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Microbiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Liu, Jianming

Contributors dc:contributor

• Kaufman, Stephen J.

• Biology, Molecular

Language dc:language

eng

Identifier

(MiAaPQ)AAI3290300

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/86698