Activators of peroxisome proliferator-activated receptor alpha (PPAR alpha) protect UV-induced changes of MMP-1 and procollagen via catalase induction in human skin fibroblasts

Abstract

We have reported that among the antioxidant enzymes, the activity of catalase decreased significantly in the dermis of photoaged and aged skin. Therefore, we suggested that the induction of catalase expression may offer a good strategy for the treatment and prevention of aging and photoaging in human skin. PPARα is a nuclear receptor involved in transcriptional regulation of lipid metabolism, fatty acid oxidation, and glucose homeostasis. In addition, PPARα activation stimulates the expression of antioxidant enzymes such as catalase. In this study, we examined whether PPARα activator modulates the expression of MMP-1 and procollagen through catalase regulation in human skin fibroblasts. We found that PPARα and catalase mRNA levels were significantly decreased by UV irradiation and in the aged skin fibroblasts. Treatment with PPARα agonists, bezafibrate and Wy14643, increased protein, mRNA and activity of catalase in dermal fibroblasts. PPARα activators, bezafibrate and Wy14643, inhibited the UV-induced MMP-1 expression and recovered the UV-induced decrease of procollagen expression. Also, in aged dermal fibroblasts, Wy14643 decreased the expression of MMP-1 and increased the levels of procollagen and catalase. Furthermore, UV-induced ROS was decreased by PPARα activator, Wy14643. These results suggest that up-regulated catalase by PPARα activation might scavenge the UV-induced ROS. Transfection with PPARα siRNA decreased catalase level and abolished all beneficial effects of Wy14643 in dermal firboblasts. In summary, our data indicate that PPARα activator increases the antioxidant enzyme catalase, leading to scavenging ROS, and protects the skin from UV irradiation as well as intrinsic skin aging process. Therefore, we propose that the PPARα activator would be a good candidate to prevent and treat skin aging.