The matrix metalloproteinase and tissue inhibitors of metalloproteinase balance in physiological and pathological remodeling of skeletal muscles

Abstract

Skeletal muscle is a highly plastic tissue that undergoes physiological or pathological remodeling in response to various stimuli such as exercise, immobilization, injury, disease, or aging. This remodeling process implies subtle or more profound changes to skeletal muscle structure and composition that involves extracellular matrix (ECM) degradation by matrix metalloproteinases. The balance between matrix metalloproteinases (MMPs) and their physiological inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), regulates tissue homeostasis. Upregulation of MMPs and/or TIMPs correlates with vascular growth and enlargement in endurance-exercised individuals or with inflammation and regeneration of muscle fibers in injured or diseased muscles. They, further, contribute to the development of fibrosis by regulating cytokine/chemokine production and release/activation of growth factors. Those induce phenotypic transformation and favor the production of ECM components. It is, therefore, important to define the exact pattern of MMP/TIMP expression and regulation in normal and diseased muscles in order to identify potential targets for therapeutic approaches or biomarkers for specific disease entities and therapeutic follow-up.