PAI-1, the Plasminogen System, and Skeletal Muscle

The plasminogen system is a critical proteolytic system responsible for the remodeling of the extracellular matrix (ECM). The master regulator of the plasminogen system, plasminogen activator inhibitor-1 (PAI-1), has been implicated for its role in exacerbating various disease states not only through the accumulation of ECM (i.e., fibrosis) but also its role in altering cell fate/behaviour. Examination of PAI-1 has extended through various tissues and cell-types with recent investigations showing its presence in skeletal muscle. In skeletal muscle, the role of this protein has been implicated throughout the regeneration process, and in skeletal muscle pathologies (muscular dystrophy, diabetes, and aging-driven pathology). Needless to say, the complete function of this protein in skeletal muscle has yet to be fully elucidated. Given the importance of skeletal muscle in maintaining overall health and quality of life, it is critical to understand the alterations-particularly in PAI-1-that occur to negatively impact this organ. Thus, we provide a comprehensive review of the importance of PAI-1 in skeletal muscle health and function. We aim to shed light on the relevance of this protein in skeletal muscle and propose potential therapeutic approaches to aid in the maintenance of skeletal muscle health.