Peroxisome proliferator-activated receptor-δ-mediated upregulation of catalase helps to reduce ultraviolet B-induced cellular injury in dermal fibroblasts

Background: Previous studies suggested that the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-delta plays an essential role in cellular responses against oxidative stress. Objective: To investigate how PPAR-delta elicits cellular responses against oxidative stress in primary human dermal fibroblasts (HDFs) exposed to ultraviolet B (UVB). Methods: The present study was undertaken in HDFs by performing real-time polymerase chain reaction, gene silencing, cytotoxicity and reporter gene assay, analyses for catalase and reactive oxygen species, and immunoblot analyses. Results: The PPAR-delta activator GW501516 upregulated expression of catalase and this upregulation was attenuated by PPAR-delta-targeting siRNA. GW501516-activated PPAR-delta induced catalase promoter activity through a direct repeat 1 response element. Mutation of this response element completely abrogated transcriptional activation, indicating that this site is a novel type of PPAR-delta response element. In addition, GW501516-activated PPAR-delta counteracted the reductions in activity and expression of catalase induced by UVB irradiation. These recovery effects were significantly attenuated in the presence of PPAR-delta-targeting siRNA or the specific PPAR-delta antagonist GSK0660. GW501516-activated PPAR-delta also protected HDFs from cellular damage triggered by UVB irradiation, and this PPAR-delta-mediated reduction of cellular damage was reversed by the catalase inhibitor or catalase-targeting siRNA. These effects of catalase blockade were positively correlated with accumulation of reactive oxygen species in HDFs exposed to UVB. Furthermore, GW501516-activated PPAR-delta targeted peroxisomal hydrogen peroxide through catalase in UVB-irradiated HDFs. Conclusion: The gene encoding catalase is a target of PPAR-delta, and this novel catalase-mediated pathway plays a critical role in the cellular response elicited by PPAR-delta against oxidative stress. (C) 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Automated summary

This study reveals that PPAR-delta plays a role in protecting HDFs against oxidative stress induced by UVB by upregulating catalase expression. By modulating catalase activity and expression, PPAR-delta counteracts UVB-induced reductions in catalase activity and protects HDFs from cellular damage.