Induction of Cellular Senescence by Secretory Phospholipase A₂ in Human Dermal Fibroblasts through an ROS-Mediated p53 Pathway

Abstract

Secretory phospholipase A₂ (sPLA₂) is involved in various cellular physiological and pathological responses, especially in inflammatory responses. Accumulating evidence suggests that inflammation is an underlying basis for the molecular alterations that link aging and age-related pathological processes. However, the involvement of sPLA₂ in cellular senescence is not clear. In this study, we found that sPLA₂ treatment induces cellular senescence in human dermal fibroblasts (HDFs), as confirmed by increases in senescence-associated β-galactosidase activity, changes in cell morphology, and upregulation of p53/p21 protein levels. sPLA₂-induced senescence was observed in p16-knockdown HDFs and p16-null mouse fibroblasts, but not in p53-knockdown HDFs and p53-null mouse fibroblasts. Treatment with sPLA₂ increases reactive oxygen species (ROS) production, and an antioxidant, N-acetylcysteine, inhibits sPLA₂-induced cellular senescence. These results suggest that sPLA₂ has a role in cellular senescence in HDFs during inflammatory response by promoting ROS-dependent p53 activation and might therefore contribute to inflammatory disorders associated with aging.

Cell aging, Secretory PLA₂, Inflammation, p53, ROS