Functionally similar genes exhibit comparable/similar time-course expression kinetics in the UV-induced photoaged mouse model

Abstract

Skin photoaging induced by ultraviolet (UV) irradiation contributes to the formation of thick and coarse wrinkles. Humans are exposed to UV light throughout their lives. Therefore, it is crucial to determine the time-sequential effects of UV on the skin. In this study, we irradiated the mouse back skin with UV light for eight weeks and observed the changes in gene expressions via microarray analysis every week. There were more downregulated genes (514) than upregulated genes (123). The downregulated genes had more functional diversity than the upregulated genes. Additionally, the number of downregulated genes did not increase in a time-dependent manner. Instead, time-dependent kinetic patterns were observed. Interestingly, each kinetic cluster harbored functionally enriched gene sets. Since collagen changes in the dermis are considered to be a major cause of photoaging, we hypothesized that other gene sets contributing to photoaging would exhibit kinetics similar to those of the collagen-regulatory genes identified in this study. Accordingly, co-expression network analysis was conducted using 11 well-known collagen-regulatory seed genes to predict genes with similar kinetics. We ranked all downregulated genes from 1 to 504 based on their expression levels, and the top 50 genes were suggested to be involved in the photoaging process. Additionally, to validate and support our identified top 50 gene lists, we demonstrated that the genes (FN1, CCDC80, PRELP, and TGFBR3) we discovered are downregulated by UV irradiation in cultured human fibroblasts, leading to decreased collagen levels, which is indicative of photoaging processes. Overall, this study demonstrated the time-sequential genetic changes in chronically UV-irradiated skin and proposed 50 genes that are involved in the mechanisms of photoaging.