For a list of our past and
current publications, click
Our agenda highlights
the following themes:
I. Role of the α7β1 integrin as an adhesion molecule in skeletal muscle that protects against injury and regulates exercise-induced muscle growth
Objective | The α7β1 integrin is a heterodimeric transmembrane receptor that links the extracellular matrix (ECM) on the outside of muscle fibers to the actin cytoskeleton on the inside of muscle fiber. Our laboratory has demonstrated that eccentric exercise can increase α7 integrin RNA (Boppart, 2008) and protein in skeletal muscle, and that overexpression of the α7 integrin inhibits strain-induced c-jun NH2 terminal kinase (JNK) activity (Boppart, 2006). Since JNK is associated with muscle injury and insulin resistance, α7 integrin-mediated inhibition of JNK may provide physiological and metabolic advantages to skeletal muscle.
Our laboratory currently utilizes several lines of genetically modified mice and primary cell lines to examine the role of the integrin in altering the intracellular molecular response to exercise and mechanical strain, particularly signaling pathways known to protect against injury and induce protein synthesis and muscle growth (MAPK's, insulin/IGF) (Lueders and Boppart, 2011; Zou and Boppart, 2011).
II. Role of the α7β1 integrin in the appearance of stem cells in skeletal muscle
Stem cells other than satellite cells, including mesenchymal stem cells and pericytes, localize to the vascular niche in skeletal muscle and contribute to muscle repair following injury. Muscle resident mesenchymal stem cells are limited in their abundance, and thus, current research is focused on identifying molecules or techniques that can increase recruitment of these cells to muscle. Methods that exploit endogenous molecular mechanisms for increased recruitment of regenerative stem cells are especially advantageous since they can bypass graft vs. host interactions associated with myoblast or satellite cell transplantation. Our current research is focused understanding the relationship between the integrin, mechanical loading, and increased mesenchymal stem cell accumulation in skeletal muscle for enhanced regeneration (Valero, 2012).
Role of the α7β1 integrin and mesenchymal stem cells in the prevention of age-related disabilities
The α7β1 integrin is a critical transmembrane linkage protein in skeletal muscle that has been shown to ameliorate disease symptoms and extend longevity in mice with a severe form of muscular dystrophy (Burkin, 2001). The extent to which loss of the α7 integrin serves as the basis for age-related decrements in muscle mass and function is not known. Our current research is focused on understanding whether integrin expression declines with age and whether restoration of integrin expression and/or function can ameliorate age-related loss of muscle mass and strength. Since mesenchymal stem cells appear in muscle in a manner dependent on the integrin, we are also evaluating the extent to which muscle-derived mesenchymal stem cell transplantation can maintain function in aged mouse skeletal muscle.