Intracellular degradation of elastin by cathepsin K in skin fibroblasts--a possible role in photoaging.

Solar elastosis is observed in the dermis of photoaged skin and is characterized by an accumulation of abnormal elastin in the extracellular space. Several proteases that degrade elastin in the extracellular space have been implicated in its formation. The lysosomal protease cathepsin K (catK) has recently been described to be highly expressed in skin fibroblasts under certain pathologic conditions. As cat K is one of the most potent mammalian elastases, we hypothesized that catK-mediated intracellular elastin degradation may play a role in the formation of solar elastosis. Immunostaining of cultured skin fibroblasts incubated with labeled elastin demonstrated internalization of extracellular elastin to lysosomes and its degradation by catK. Induction of catK expression in fibroblasts was observed both in vitro and in vivo after exposure to longwave UVA. In contrast to fibroblasts from young donors, cells from old donors failed to activate catK in response to UVA. These data suggest a role of intracellular elastin degradation by catK in the formation of solar elastosis. We propose that an age-related decline in catK activity, in particular after UV exposure, may promote the formation of actinic elastosis through a decline of orderly intracellular elastin degradation and subsequent accumulation of elastin in the extracellular space.