Involvement of IGF binding protein 5 in prostaglandin E2-induced cellular senescence in human fibroblasts

Abstract

Inflammation is an underlying basis for the molecular alterations that link aging and age-related pathological processes. In a previous study, we found that secretory phospholipase A(2) (sPLA(2)) induced cellular senescence in human dermal fibroblasts (HDFs). To further investigate the association of inflammation with cellular senescence, the effects of PGE(2) on cellular senescence in HDFs were investigated, since PGE(2) is the most abundant prostanoid. PGE(2) treatment induces cellular senescence, as determined by a decrease in cell proliferation and an increase in senescence-associated β-galactosidase staining. Notably, PGE(2) treatment increased the IGFBP5 protein level. While treatment with PGE(2) antagonists repressed PGE(2)-induced cellular senescence, increasing intracellular cAMP accelerated cellular senescence. Down-regulation of IGFBP5 inhibited PGE(2)-induced cellular senescence. Taken together, these results suggest that PGE(2) may play an important role in controlling cellular senescence of HDFs through the regulation of IGFBP5 and therefore may contribute to inflammatory disorders associated with aging.