Ageing effects on the expression of cell defence genes after UVA irradiation in human male cutaneous fibroblasts using cDNA arrays

Abstract

Ageing is a multifactorial process in which reactive oxygen species (ROS) are thought to be implicated. ROS cause oxidative alterations on cell constituents, and damage accumulation can lead to mutations in DNA. Modulation of gene expression during ageing is now quite documented but results are often controversial and/or incomplete. As ultraviolet A is one of the exogenous factors involved in skin ageing, by the production of ROS, we further document the modifications in gene expression during ageing process and response to an oxidative stress. For this purpose, we used a cDNA macroarray containing 82 genes related to cell defence, essentially represented by antioxidant and DNA repair proteins. Ageing-associated gene expression was assessed in normal skin human fibroblasts from three age groups: children (n=4), adults (n=4) and olders (n=3), at the basal state and after a 5J/cm2 UVA irradiation. Analysis revealed that 22 genes were never detected, whereas certain were always expressed such as those related to antioxidant defence, extracellular matrix (ECM) regulator and XPC. Transcripts related to ECM, MMP1 and MMP3 were increased with age and after UVA irradiation, independently of age. It appeared that transcripts involved in the redox status control (TXN and APEX) decreased as a function of age, at the basal state and after irradiation, respectively. Most of transcripts involved in DNA repair were not detected but repression of POLD1 in the adult group and induction of XRCC5 and LIG4 were observed after UVA irradiation, as a function of age. In the basal state, the transcript of GAS1, regulator of cell cycle arrest in G1 phase was found to be decreased with age. HMOX1 increased after UVA irradiation. In conclusion, the decrease in expression of some antioxidant system, cell cycle control gene and extracellular matrix enzymes, particularly after UV exposure can explain the occurrence of photoaging.