The calpain system as a potential target for pelvic muscle reinforcement

The fascial and muscular components within the pelvic floor create a support mechanism that facilitates storage and voiding of urine. Their constituents are mainly fibrillar collagens I and III, which are responsible for maintaining tensile strength. Stretching and recoiling is enabled by the elastic fibers consisting of elastin on a scaffold of microfibrils, fibrillin-1 and -2. Calpains are intracellular Ca2+ -dependent cysteine proteases found in almost all eukaryotes and some bacteria. Calpains display limited proteolytic activity at neutral pH, proteolyzing substrates to transform and modulate their structures and activities, and are therefore called “modulator proteases”. By making selective limited proteolytic cleavages, they modulate the activity of enzymes, including key signaling molecules, and induce specific cytoskeletal rearrangements, accounting for their roles in signal transduction and structural stabilization. Understanding these mechanisms should provide avenues for novel therapeutic strategies to treat pathological processes such as urinary incontinence and pelvic prolapse.