Caspase-3-mediated α-smooth muscle actin cleavage during staurosporine-induced myofibroblast apoptosis

To examine the possibility that staurosporine is applicable for the treatment of abnormal scar formation such as hypertrophic scar and keloid, the cellular process during staurosporine-induced apoptosis was analyzed in myofibroblasts isolated from a rat granulation tissue pouch. Staurosporine induced myofibroblast apoptosis in a time- and a dose-dependent manner with typical morphological changes. Staurosporine activated caspase-3 up to 3.6-fold by cleaving pro-caspase-3 to active forms. Alpha-smooth muscle actin was degraded during staurosporine-induced apoptosis. The degradation of α-smooth muscle actin was detected at an early stage of staurosporine-induced apoptosis. Recombinant active caspase-3 and staurosporine-stimulated caspase-3 both cleaved purified α-smooth muscle actin in vitro. These results suggested that α-smooth muscle actin is directly degraded by caspase-3 in response to apoptotic stimuli in myofibroblasts.